Activity Report 2007

Transcription

Activity Report 2007
Table of contents
Activity report cover:
The fate of MSCs injected into allogeneic intervertebral discs is tracked by
red fluorescence membrane dye. The
laser scanning image shows a cell
cluster of red MSCs. Disc tissue was
labeled with calcein green for living
cells and DAPI for nuclei. Yellow cells
(= co-labeling of green and red) mark
living MSCs and green cells mark living
endogenous disc cells. Thus, this triple
stain technique allows determination
of cell viability of both, exogenous and
endogenous cells alike.
| Activity Report 2007
1. Introduction
3
2. Programs
4
3. Institutional and Professional Relationships
9
4. Good News
11
5. Project Abstracts
13
6. Team Members
40
7. Publications
43
8. Presentations
48
1. Introduction
Since 1997, the staff of the AO Research Institute published a total of 432 peer-reviewed manuscripts. These papers document in a sustainable manner our scientific findings. They added significant data to the general knowledge regarding the
function of the musculo-skeletal system. During the past 10 years, 5 habilitations and 153 theses or doctoral dissertations
were accepted by a variety of University Faculties. This underlines the excellent academic quality of the institute, which is
recognized by other peers in the field. The AO thereby has been able to boost the personal careers of many scientists as well
as medical or veterinary doctors. Another sign of quality and respect from the scientific community were the 60 awards
bestowed on members of the institute, ranging from student awards to lifetime recognition of significant work. Employees
spent endless hours to prepare the 1‘475 presentations delivered at a multitude of conferences, symposia and meetings. All
of them did their best to convince the audience not only of the high calibre research performed, but they also were ambassadors strengthening the profile of the AO Foundation in the world. Each year, about 30 scientists left the institute to
move forward in their careers. These 339 highly trained individuals continue to have close bonds to the AO and now form
a benevolent international network of AO Friends. Another large group of scientists was motivated to consider our work
when they agreed to present at or at least participate in one of the 18 conferences organized by the AO Research Institute.
The ensuing discussions stimulated new, important research projects, fostered collaboration with other groups and made
the institute an attractive hub for open exchange of novel ideas. It also helped the AO to take timely decisions.
The members of the team worked on a variety of topics such as animal models, bone and implant biomechanics, cartilage
tissue engineering, defect treatment, development and characterization of biomaterials, disc degeneration and regeneration, fracture fixation in osteoporotic bone, fracture healing and treatment, infection, implant surfaces and tissue interfaces, tissue histomorphometry and immunohistochemistry, understanding and interaction of stem and tissue cells in tissue
engineering. Some of these were highly applauded by experts in the field, some were service tasks for customers.
Which of these activities has been the most important one? We will not know until the future has become the present. And
the answer may also be different depending on who will be giving the answer. We have all given our very best, because
we are convinced, that the research capacities, expertise and experience in Davos are one of the assets of the AO for the
future.
I wish to express my sincere gratitude to each individual member of the team for his dedication,
valuable work, intellectual input and service provided at any time. I also wish to thank the chairmen
and members of the different boards for their guidance, support and friendship.
Prof. Dr. Erich Schneider
Director
2. Programs
Biomaterials and Tissue Engineering
Program Leader: Mauro Alini
Polymers
Bone
Cartilage
Head: Mauro Alini
Members:
Marco Agnello
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Yuting Chen
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Jessica Denom
David Eglin Christoph Forkmann
Markus Glarner
Sibylle Grad
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Franziska Greulich
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Stéphane Griffon
Sven Hoppe
X
Laszlo Kupcsik
X
Judith Langeraar
X
Zhen Li X
Sebastian Lippross
X
Anna Morys
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Damien O’Halloran
Robert Peter
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Urs Schlegel
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David Senn
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Martin Stoddart
Sophie Verrier
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The Biomaterials and Tissue Engineering program focuses on two major
research areas: bone and cartilage regeneration. The team develops biological
approaches addressing pathologies of the musculoskeletal system, with a particular
focus on bone and cartilage tissues. The ultimate goal is to define strategies for prevention of
degenerative disorders of the skeleton and to re-establish its functionality.
Goal 1
To regenerate bone and cartilage defects using resorbable-biodegradable scaffolds and
tissue engineering approaches. The objectives are first: the refinement of resorbable
polyurethane scaffolds via the tailoring of
their physical and chemical properties, and
secondly, the design and preparation of biodegradable hydrogel/polyurethane hybrid
scaffolds for the improvement of the cellmaterial interactions.
Goal 2
To gain understanding of selected problems
associated with cartilage repair in a tissue engineering approach. The research focuses on
mesenchymal stem cell differentiation into
chondrocytes grown in 3-D biodegradable
polymers. Strategies to induce and maintain
the correct chondrocytic phenotype expression include the modification of the scaffold (chemical composition, pore size), low
oxygen tension and also the mechanical
stimulation of the chondrocyte-seeded polymer by the application of defined regimes
of dynamic strain and surface motion under
highly controlled conditions.
Mechano-Biology
Program Leader: Keita Ito
Intervertebral Bone Disc
Healing
Head: Keita Ito
Members:
Michelle Baucke
Samantha Chan
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Benjamin Gantenbein
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Ina Gröngröft
X
Hanna Isaksson
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Svenja Jünger
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Patrick Lezuo
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Jérôme Noailly
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Esther Potier
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Melanie Pucher
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Andrea Tami
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Marije Van Der Werf
Sandra Wissing
Stephan Zeiter
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Intervertebral Disc
The aim is to understand the basic mechanisms and implications of intervertebral
disc degeneration and to develop long-term
functional treatments.
It is generally believed, that degenerative disc
disease is one of the most prevalent causes
of low back pain. However, its causes and
pathophysiology remain poorly understood.
The strategy focuses on exploring deficient
nutrition and mechanical loading as mechanisms of disc degeneration, analyzing the
biomechanical characteristics of normal and
degenerated discs, and to provide a basis for
tissue engineering approaches towards disc
replacement and regeneration. In terms of
regenerative approaches, bone-marrow derived stromal cells and growth factors are
currently investigated.
Bone Healing
The goal is to elucidate mechano-transduction
in fracture healing by combining in vivo studies, in vitro models and finite element analyses of the biological tissues and processes.
Fracture healing is a regenerative process
whose progress is influenced by its mechanical environment. Bone is one of the few tissues in our body, which can regenerate rather than repair. After injury, adult pluripotent
progenitor cells are stimulated to differentiate and eventually reproduce bone through
Fracture
Treatment
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processes similar to those during embryonic
development. These complex processes are
governed by cells communicating via growth
factors and cytokines and may be influenced
by the local physical environment.
Our aim is to improve the knowledge of
these mechano-transduction mechanisms
on both the biomechanical and biological
level. This knowledge will then be used to
develop future implants and treatments.
Fracture Treatment
The purpose is to investigate fracture treatment and to improve fixation in osteoporotic bone.
Although the magnitude of the problems associated with osteoporotic fractures is evident, our ability to treat these fractures with
internal fixation remains limited. The complications of healing are often of high morbidity with some socio-economic impact.
Furthermore, the incidence and severity of
fractures in the aged has increased significantly and will continue to do so. Utilizing
the core competence of AO in fracture treatment as well as our basic knowledge gained
from fundamental investigations, we are concentrating on mechanical, chemical and/or
biological technologies for better implant anchorage. Thus, our aim is to reduce or avoid
such complications and to accelerate healing
in both osteoporotic and normal bones.
Bioperformance of Materials and Devices
Program Leader: R. Geoff Richards
Interface Biology Group Tissue Morphology & Histology Group
Head: R. Geoff Richards
Head: Stefan Milz
Members:
Pamela Furlong-Jäggi
Members: Volker A. Braunstein
Jessica Hayes
Mauro Bluvol
Katharina Jähn
Sven Duda
Fintan Moriarty
Nora Goudsouzian
Alexandra Pearce
Marianne Leumann
Alexandra Poulsson
Andrea Oswald
Christoph Sprecher
This program includes two separate functions, Interface Biology and Tissue Morphology.
Interface Biology performs applied translational research to investigate cell, tissue
and bacterial reactions to biomaterial surfaces in vitro, ex vivo, and in vivo for implementation within AO approved implants according to goals 1 and 2. Tissue Morphology and histology performs histological based projects for internal and external partners.
Goal 1
To control implant-tissue interactions with
implant surface modification.
Vascularisation and securely attached connective tissue (bone or soft tissue) at the implant surface are often desirable in internal
fixation. Direct bony integration is a requisite for long-term implants and prostheses,
and is important in patients with osteoporosis. In some anatomical areas such as hand,
foot, shoulder and CMF, soft tissues, such as
tendons, muscles or nerves must freely glide
over the implant surface for normal function.
For temporary implants including screws,
plates and nails it is preferable also to control the amount of direct osseointegration to
allow easier implant removal after fracture
healing. Surface treatments are developed
and tested to answer these problems, while
maintaining the implant biocompatibility.
New non-metallic materials used for X-Ray
translucency, especially in areas such as the
spine are also having surface modifications
applied and tested.
Goal 2
To increase implant infection resistance
through surface modification and implant
design.
Infection in fracture fixation remains a major problem. One of the three key features
of susceptibility to infection is the actual nature of the device used. The device nature
includes – among others – biocompatibility
of the material or materials used (especially
the interacting surface); whether the device
promotes or inhibits tissue adhesion and / or
bacterial growth; surface properties; shape
and design including number of possible
“dead spaces”; function, whether the device
is temporary or long-term, and whether the
implant is adjacent to moving tissues. Accordingly, surfaces and design have been
evaluated to either reduce initial bacterial
attachment or to inhibit entry to “dead spaces”.
Tissue Morphology & Histology
Tissue Morphology & Histology provides collaborative research and services, which include routine paraffin histology as well as
hard and soft tissue histology with and without implant materials. For immunohistochemistry and immunocytochemistry several
techniques are available, such as peroxidase
and/or phosphatase detection, immuno-fluorescence, double, triple and multi label detection, gold-labelling with silver enhancement and Technovit embedding of small
samples. Microscopic investigations can be
performed using conventional transmitted
and several reflected light methods including fluorescence and confocal microscopy.
Image analysis (2-D and 3-D) is available
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for all instruments. Surface characterisation
techniques include white light profilometry
for quantitative data, Scanning Electron Microscopy (SEM) for material morphological
analysis as well as routine elemental determination using Energy Dispersive X-Ray Microanalysis (EDX). SEM techniques developed internally for biomaterial, cell, tissue
and bacterial interface studies include low
voltage backscattered electron imaging and
immunogold labelling of surface antigens.
1 Microradiograph of sectioned human
vertebra 3 years after vertebroplasty.
The orange labelled area indicates
the PMMA cement distribution in the
meshes of the cancellous bone. The
PMMA block is surrounded by a zone
of newly formed woven bone that
strengthens the interface between
stiff bone cement and relatively elastic
cancellous bone.
2 Comparison of gap osteotomy bone
healing in mice stabilized using a
flexible fixation with and without additional periosteal damage. MicroCT
results confirmed that after the same
duration of healing, those without
periosteal damage had much more
immature woven bone. (21d post-op:
a – with periosteal injury; b – without
periosteal injury / gray= lamellar bone;
green= woven bone).
3 Immunostaining using a Laminin specific antibody on bone marrow mononuclear cells fraction after removal of
CD34+ and CD133+ EPC cells.
4 Under exclusion of the implant head,
each bone was partially embedded in
a PMMA filled mold. The implant head
was held firmly in a custom made
jig, which itself was connected to the
testing machine (Instron, Darmstadt,
Germany). The implant was then
pulled under displacement control
(1mm/min) until failure so that peak
and ultimate force could be determined.
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Histological services were provided for more
than 55 projects in 2007. Services comprised
the preparation of more than 1‘650 immunohistochemically labelled slides and more
than 5‘000 cryocuts. Undecalcified bone and
implant histology involved the resin embedding and cutting of more than 5‘600 sections
with special saw microtomes. 1‘700 paraffin
sections were obtained for conventional histology.
Contract Research & Support
Program Leader: Simon Pearce
Experimental Surgery Group
Research Services Group
Head: Simon Pearce
Head: Karsten Schwieger
Members:
Daniel Arens
Members:
Romeo Accola
Ludovic Bouré
Vittoria Brighenti
Laurence Debefve
Stefano Brianza
Declan Devine
Benno Dicht
Peter Erb
Boyko Gueorguiev
Pierina Faoro
Bas van der Pol
Andrea Furter
Dieter Wahl
Joachim Hahn
Markus Windolf
Tina Kaltenbrunner
Katharina Kluge
Urban Lanker
Michael Leitner
Gregor Müller
Reto Müller
Dominik Perren
Livia Poser
Georg Rindermann
Catherine Ruegg-Moser
Ulrike Seidenglanz
Elsbeth Wenzinger
Muriel Wieling
Tanja Witte
Stephan Zeiter
The program comprises the two technical
groups „Experimental Surgery“ (in vivo
experiments) and „Research Services“ (expertise for in vitro studies). The program
renders research services within and outside the AO Foundation. Both groups have
the knowledge, skills and experience to
assist researchers in a modular manner,
starting with project design and ending with
data analysis and publication. Our services
include surgery, animal care, mechanical
testing, CT-analysis, statistics, literature, machine shop and general laboratory support.
In addition, consulting can be provided, especially with respect to experimental questions and development of methods.
The main partners for collaborative projects
are the Research Institute and the Development Institute of the AO Foundation,
clinicians, industrial partners, and several
external academic institutions.
The Goals of the Program are:
• To support the research programs of the
AO Foundation with their clinical focus.
• To answer questions from clinicians and
industrial partners to improve fracture
fixation devices or surgical procedures.
• To inspect new technologies of potential
relevance for the AO Foundation.
• To provide a research environment and
support career development for clinicians.
• To collaborate with external academic institutions on research projects that fulfil
the mission of the AO Foundation.
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3. Institutional and Professional Relationships
AO Research Board
The AO Research Board oversees all research
related activities of the AO Foundation. This
body is responsible for the AO Research Institute, for the AO Research Fund and for
the Collaborative Research Centers (CRCs).
CRCs in 2007 were the Research Laboratory,
Trauma and Reconstructive Surgery, Charité, Berlin, as well as the Institute for Clinical
and Experimental Surgery with the Department of Trauma, Hand and Reconstructive
Surgery, University of Saarland, Homburg. A
new CRC may be added in 2008.
Chairman of the AO Research Board is N. Südkamp (Freiburg i.Br.
Germany). The members in 2007 were S. Buchman (Ann Arbor MI,
USA), K.M.C. Cheung (Hong Kong, China), B. Hanson (Dübendorf,
Switzerland. Director AO Clinical Investigation and Documentation),
P. Hoffmeyer (Geneva, Switzerland), K. Kocher (Zürich, Switzerland),
A.R. Poole (Montreal, Canada), M. Rauh (Davos, Switzerland, Chairman AO Board of Directors), E. Schneider (Davos, Switzerland, Director AO Research Institute), S. Steiner (Davos, Switzerland, Manager
AO Research), G. Strasser (Davos, Switzerland, CEO AO Foundation),
A. Sugar (Swansea, UK, Chairman AO Research Fund), C. van der
Werken (Utrecht, Netherland, President AO Foundation), Brigitte von
Rechenberg (Zürich, Switzerland).
1 The fate of MSCs injected into allogeneic intervertebral discs is tracked by
red fluorescence membrane dye. The
laser scanning image shows a cell
cluster of red MSCs. Disc tissue was
labeled with calcein green for living
cells and DAPI for nuclei. Yellow cells
(= co-labeling of green and red) mark
living MSCs and green cells mark living
endogenous disc cells. Thus, this triple
stain technique allows determination
of cell viability of both, exogenous and
endogenous cells alike.
2 Immunolocalization of keratin-19 in
nucleus pulposus of rat coccygeal disc.
Bar = 0.1mm.
3 Effect of surface topography on osseintegration- cancellous bone.
4 Fibrin carrier produced as cylinder with
a diameter of 8 mm and a height of
4 mm. Effects of calcium, chloride and
factor XIII concentrations on turbidity
and homogeneity were evaluated by
image analysis.
University and Professional Relationships
Mauro Alini is an Assistant Professor at the
Division of Surgery of the McGill University, Montreal, Canada and Professor (incaricato) at the Faculty of Science, Division of
Biotechnology, of the University of Genoa.
Since 2005, he serves as Board Member of
The Swiss Bone and Mineral Society and as
member of the Award Committee for The
GRAMMER European Spine Journal Award.
In 2007 he became a Board Member of the
Membership Committee of the Orthopaedic
Research Society. He is a member of the
Scientific Editorial Board of the European
Cells & Materials Journal. He was also elected to the Editorial Board of BioMed Central
Musculoskeletal Disorders and to the Open
Orthopaedic Journal, both online journals,
as well as to the Advisory Board of the Archives of Orthopaedic and Trauma Surgery.
Stefan Milz is a member of the Medical Faculty of the Ludwig- Maximilians University
of Munich, Germany. He has an appointment as lecturer at the Department of Anatomy (Kurs Makroskopische Anatomie I Präparierkurs) and takes part in seminars and
in supervising the anatomical dissections. He
is also acting as a Receiving Editor for the
Journal of Anatomy, which is a major international journal that carries articles contributing to the understanding of biological
development, evolution and function.
Keita Ito has moved to Eindhoven University of Technology in the Netherlands in 2007.
He was appointed Professor and Head of the
Biomechanics Section in the Department of
Biomedical Engineering. He is President of
the European Society of Biomechanics and
Co-Survey-Editor for the Joural of Biomechanics. He is also a member of the Editorial
Advisory Board of the European Spine Jour-
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nal and a Consulting Editor for the Journal
of Orthopaedic Trauma.
Berton Rahn continued to support us in the
highly appreciated function of a scientific
advisor with his long-term experience and
expertise in the histological evaluation of
tissues.
R. Geoff Richards has appointments as Honorary Professor at Cardiff School of Biosciences, Cardiff University, Wales, GB and at
the Institute of Biological Sciences, Aberystwyth University, Wales, GB. He is an honorary senior research fellow in the Division
of Infection and Immunity, University of
Glasgow, GB. Geoff has one year remaining
of a three year Visiting Professorship at the
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University,
Japan. He is Editor-in-Chief of the European
1 Illustration of surgical approach to
the rat tibia. The titanium screws and
surgical device have been applied on
the tibia.
2 Rats were ovariectomized and after
4 weeks their osteoporotic state was
verified with in vivo bone mineral density (BMD) measurements. Titanium
screws (Ø1.7 x 5mm) were implanted
bilaterally into the proximal tibial
metaphysis of each rat using a custom
made surgical device. In the right tibia,
the drill-hole was filled with HA ceramic
particles (60–100 μm) before screw
insertion. The left tibia was without HA
particles (control).
3 Immunostaing using antibody against
von Willebrand factor on CD34+
selected cells after 21 days of culture
in presence of PRGF.
4 AFM image displaying surface topog-
raphy of untreated non degradable
polymer PEEK, as used in spine cages.
10 | Activity Report 2007
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Cells & Materials Journal, is President of the
Swiss Society of Biomaterials and a member
of the Scientific Advisory Board of the Biomaterials Network.
Erich Schneider is a member of the Faculty
of Mechanical Engineering of the Technical
University Hamburg-Harbug, Germany. He
has an appointment at the Medical Faculty
of the University of Basel, Switzerland. He is
a visiting professor at Rush University Medical School, Chicago IL, USA. He is responsible for the courses in fracture treatment for
medical students of all Medical Faculties in
Switzerland. He is a member of the Steering
Group of the National Research Program 53
of the Swiss National Science Foundation
and a member of the Executive Management of the AO Foundation. He is a Founding Member of Science City Davos and a
Board Member of Davos Health.
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4. Good News
1 Bone graft failure during spondylodesis
of the sheep spine. The bone graft is
well incorporated into the cancellous
bone of the adjacent vertebral bodies.
The midpart the bone graft is however
fractured and the mechanical situation has caused the development of
fibrocartilagious tissue in the gap.
2 Uni-axial displacement bioreactor for
mechanical stimulation of mesenchymal stem cells in fibrin carrier.
The constructs are cultured and
stimulated under unconfined compression in 6-well plates mounted
on different loading units. In a well
plate, compressive loads are equally
transmitted to each scaffold through 6
PEEK pistons that move together with
the well plate top cover according to
the motions imposed by a pneumatic
actuator. The whole bioreactor consists
of four loading units that work either
synchronised or independently. Each
6-well plate of each unit can be easily
removed for medium change under
sterile conditions.
3 Mice fracture callus remodelling. μCT
dataset after a-b) 21, c-d) 28 and e-f)
42 days of healing. The top shows
mid-sagittal cross sections, and the
lower part transverse cross-sections
through the fracture gap.
4 Microtomography reconstruction of a
biodegradable polyurethane bi-phasic
scaffold.
5 Tri-fluorescent labelling of adhesion
complexes and stress fibre organisation in S-Phase human osteoblats
on nanogrooved PMMA. (A) HOBs
cultured on planar controls formed
well-organised stress fibres and
numerous super-mature adhesions.
(B) Osteoblasts on 100 µm grooves
possessed a well-developed actin cytoskeleton. Adhesions were large and
numerous. (C) HOBs cultured on 25
µm grooves developed an organised
actin cytoskeleton. Adhesion formation
was reduced relative to planar controls.
(D) 10 µm grooves arrays disrupted
cellular spreading. Adhesion formation
was influenced by groove orientation.
Red = actin, green = vinculin, blue =
S-phase nuclei.
Congress organisation
From June 25–28, 2007, Prof R. Geoff Richards, Prof. Mauro Alini and Prof Charlie Archer held the international congress “European Cells & Materials“ ECM VIII in Davos.
The meeting theme was Bone Tissue Engineering, the second of the ECM conferences
on this theme. It was dedicated to honour
Prof. Dr. med. D.Sc. (h.c.) Stephan M Perren, ex director of the AO Research Institute,
a world-renowned research trauma surgeon
for his longstanding bone research, teaching,
advising, fostering ideas and mentoring of
scientists. The meeting started with an excellent overview of clinical problems, followed
by current research and some cutting-edge
work from the groups of Hubbel and Evans.
It finished with a look to achievements and
future work necessary from Prof. Stephan
Perren. Abstracts from the conference were
published as a supplement of the ECM Journal and are freely accessible from the AO
Website (www.ecmjournal.org).
Awards
Manus Biggs won the Young Scientist Award
at the Society for Experimental Biology, SEB
at Glasgow for his paper “The Influence of
Nanoscale Biomimetic Structures on Osteoblast Adhesion”. Co-authors are RG Richards,
N Gadegaard, CDW Wilkinson, and MJ Dalby.
Jessica Hayes was granted a travel award of
CHF 1‘000 from the Swiss Society for Bone
and Mineral Research for the European Society for Biomaterials Conference, Brighton,
September 2007 for her oral presentation on
“The Potential of Surface Polishing for Elective Internal Fixator Retrieval”. Co-authors
are CW Archer and RG Richards.
Katharina Jähn was granted a travel award
of CHF 1‘000 from the Swiss Society for
Bone and Mineral Research for the European Society for Biomaterials Conference,
Brighton, September 2007 for her oral presentation on Osteocyte Viability and Influence of Culture Conditions on Ex Vivo Human Cancellous Bone. Co-authors are MJ
Stoddart, PI Furlong, CW Archer, and RG
Richards. She won the “Best Poster” award
for her contribution “Effect of a serum free
medium containing TGF-ß3 on osteocyte viability of cultured human cancellous bone
explants” to the Swiss Society for Biomaterials Conference, Neuchatel, May 9th 2007.
Co-authors were MJ Stoddart, PI Furlong,
DB Jones, CW Archer, and RG Richards.
Katharina also won the Novartis SBMS best
Fundamental Research Presentation for her
contribution “Effect of serum free medium
on osteocyte viability in ex vivo cultured human cancellous bone explants” to the 13th
Annual SBMS & SVGO / ASCO Meeting at
Uniklinik Balgrist in Zurich. Co-authors are
MJ Stoddart, PI Furlong, CW Archer, and
RG Richards.
Alexandra Pearce won the Novartis SBMS
best Translational / Clinical Presentation for
her contribution “In vivo evaluation of polished titanium and titanium alloy screws to
minimize bone adhesion” to the 13th Annual
SBMS & SVGO / ASCO Meeting at Uniklinik
Balgrist in Zurich. Co-authors are SG Pearce,
S Milz, CW Archer, and RG Richards.
David Kubosch won the best poster award
in the spine session of the 71st annual meeting of the DGU in Berlin October 24–27,
2007 with the topic “Die Diagnose des Transplantatversagens bei der ventralen lumbalen
Spondylodese: Eine Frage der Auflösung,
demonstriert am Xtreme-CT”. Co-authors
are S Milz, TA Bley, CM Sprecher, NP Südkamp, and PC Strohm.
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Extramural funding
R.G. Richards: European Space Agency Microgravity Application Program for the International Space Station, “A combined perfusion/loading chamber for bone metabolic
studies.” (01/2005–12/2007, 48’000 Euro/
year)
R.G. Richards and S. Poulsson Commercial
Funding Invibio for the project “Investigation of the behaviour of cells derived from
soft and hard tissues on surface modified
PEEK for internal fracture fixation” (2007–
2008, CHF 100‘000).
Mauro Alini, Sibylle, Grad, Martin Stoddart.
SNF Grant, 320000-116846/1, CHF 260‘000
for the project “The effect of mechanical
stimulation and biological factors on human
mesenchymal stem cells chondrogenesis and
hypertrophy”,
Grad Sibylle, Ito Keita, Zeiter Stephan, Mauro Alini. SNF Grant, 320000-116818/1, CHF
325‘520 for the project “Nucleus pulposus
and annulus fibrosus cells: Cellular phenotype characterization and in vitro differentiation from mesenchymal stem cells”.
1 Effect of surface topography on osseintegration- cortical bone.
2 Toluidine-blue (a,b,e,f) and safranin
O/fast green (c,d,g,h) stained sections
of chondrocytes-polyurethane constructs cultured at 5% or 21% oxygen
for 28 days. Bar = 1mm (a,c,e,g);
0.2mm (b,d,f,h).
3 Mouse mesenchymal cells
(C3H10T1/2) seeded in a fibrin carrier. Cells were seeded in fibrin carrier
and cultured for 1 week under static
conditions. At this time, cells were
stained with Calcein AM and observed
with confocal microscope. Shown
picture is representative of top surface
of the carrier.
Further achievements
European Cells & Materials (ECM) open access, non profit journal (www.ecmjournal.org),
with Editor-in-Chief Prof. R.Geoff Richards,
passed 5‘400 registered readers mark within
2007. ECM journal is indexed by Medline
CAS, Index Medicus, and Scopus databases
and can be searched directly from Pubmed,
DOAJ and Open J Gate. In April 2007, ECM
journal was accepted to be covered by ISI
Science Citation Indexes and will receive an
impact factor within two years.
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5. Project Abstracts
Biomaterials and Tissue Engineering Program
Goal 1
1 Procion red filled endplate vascular
buds (white arrows) and non-filled
buds (red arrows). (AAF = anterior annulus fibrosus, PAF = posterior annulus
fibrosus, NP = nucleus pulposus, Ti
= titanium foil.) a. Control, b. Experimental.
2 Immunolocalization of glypican-3 in
nucleus pulposus of rat coccygeal disc.
Bar = 0.1mm.
3 Polycarbonate bioreactor for cultivating
ovine caudal discs under loading. IVDs
with intact cartilaginous and bony endplates are maintained in a “sandwich”
between two porous stainless steel
plattens through which culture media
is slowly refreshed (120 µl /min). Gas
exchange is ensured by a permeable
silicone membrane that seals the
chamber from the top.
Synthesis of a bi-functional scaffold to
improve the integration and stabilization
of osteochondral defects
The objective of this project is to address the
issue of the functional integration and stabilization of a cartilage tissue engineered implant into the osteochondral bone. A tissue
engineering (TE) approach has been chosen,
consisting of the production a non-competent tissue, implanted together with living cells into the joint defect, which would
mature and become competent within the
natural joint environment. A fundamental
and key property of the graft is its ability to
functionally integrate within the native tissues of bone and cartilage. Therefore, it was
hypothesized that the implantation of a TE
construct with two well-defined bone and
cartilage regions could improve the integration and healing of osteochondral defects. In
order to trigger tissue growth, cells will be
seeded in the cartilage part of the construct,
while the bony part of the construct will
be populated by osteoprogenitor cells from
bleeding subchondral bone. The approach
to the preparation of bi-functional scaffolds
consisted in the design of a fully biodegradable construct based on two elastomeric
polyurethane scaffolds with optimized mechanical properties and a distinct transition
layer made of a microporous membrane. The
optimization of the structural, degradation
and mechanical properties of the biphasic
construct is in progress. The bi-phasic construct design and its ability to promote and
spatially control the bone and cartilage tissue regeneration will be validated in vitro.
Publications: Diss: 3; Pub: 14; Pres: 60, 61.
Improving the cell-polymer interaction
to facilitate cell proliferation and matrix
formation
The repair of cartilage defects via tissue engineering constructs is potentially a very effective approach to supplement the limited
regeneration capacity of cartilage and bone
and because of the various drawbacks of
the current surgical repair techniques. A fibrin/polyurethane hybrid scaffold developed
at the ARI has shown to be promising for
articular cartilage tissue engineering. Still,
there is the need to improve the scaffold
either by modifying the polyurethane, the
hydrogel or both components. Recently, impregnation of long-chain plant polyprenols
on polyurethane membranes has shown to
be beneficial for chondrocyte-material interaction in vitro, and it was proposed that
the incorporation of polyprenol molecules
into the polyurethane linear chain may be
beneficial for the cell-material interactions
and may improve the regeneration of articular cartilage tissue. Thus, the purpose of
this project was to prepare a biodegradable
polyurethane containing polyprenol molecules. A method for the bi-functionalization
of polyprenols was developed and a model
compound incorporated into biodegradable
polyurethane. The polyurethane molecular structure, its surface properties and the
biocompatibility of polyurethane films were
characterized. Scaffolds made of the modified
polyurethanes were prepared. Their threedimensional structure and their degradation
properties were assessed. Finally, chondrocytes encapsulated within a fibrin gel, seeded into the three-dimensional polyurethane
scaffolds, were cultured in vitro. The study
showed that the polyurethane scaffolds containing polyprenols affected early ECM distribution, but had no significant effect on the
chondrocyte survival, proliferation and ECM
production when compared to unmodified
polyurethane scaffolds. The effect on the
ECM distribution was tentatively attributed
to the change in scaffold architecture as the
release of polyprenols was ruled out by the
degradation study performed. This suggested
that the hybrid fibrin/polyurethane scaffold
may have its biological response improved
further by modification of the hydrogel rather than the polyurethane.
Publications: Pres: 59.
Endothelialized grafts for bone critical
size defect treatment
Bone formation is highly dependent on the
presence of osteogenic cells at the implant
sites, but vascularisation is also a major
concern. Our general aim is to establish an
autologous bone graft made of a synthetic
scaffold, e.g. polyurethane pre-cellularised
with both endothelial cells (EC) and bone
marrow stromal cells (BMSC), which–under
autologous growth factor stimulation using
Platelet Rich Plasma (PRP)–will differentiate
into mature endothelial and osteoblastic cells
respectively.
Our previous work using human BMSC and
human umbilical vein endothelial cells (HUVEC) co-cultured in both a 2-D system and
a 3-D construct showed further evidence of
EC – BMSC communication and co-stimulation.
This interaction was further studied by analysing the influence of the relative cell proportions (EC vs. BMSC) on the two types of
cells. The percentage of HUVEC or endothelial progenitor cells (EPC) was found to have
an influence on BMSC differentiation. In PRP
gel (3-D) we observed an up-regulation of
RUNX2, DLX5 and OSX genes when BMSC
were cultured together with EPC compared
to BMSC alone. The gene expression levels were found to be higher when 25 % of
EPC were added to MSC when compared to
higher proportions of EPC.
We further investigated the PRGF (soluble
form of PRP) mode of action at the intracellular level. In presence of PRGF stimulation,
we observed a strong BMP2 and MMP13
up regulation at the mRNA level compared
to BMSC without PRGF. Interestingly, there
was no significant up-regulation of RUNX2,
OSX and ALP mRNA (classical osteogenic
pathway). This indicates that PRGF could
stimulate BMSC differentiation in a RUNX2OSX independent manner, most probably via
BMP2 up-regulation.
Publications: Diss: 2.
Partners: A. Hofmann, Department of
Trauma Surgery, University Hospitals of
the Johannes Gutenberg University, Mainz,
Germany.
Isolation and characterization of endothelial progenitor cells
The aim of this project is to find a cell source,
which is not immunogenic (autologous cells
or stem cells), which has a high growth capability and which is able to differentiate
into mature functional endothelial cells. This
will increase the formation of blood vessels
at the injury site. Recently, accumulative evidence indicates that bone marrow as wells
as peripheral blood of adults contain endothelial progenitor cells (EPC). EPCs can be
easily isolated from bone marrow aspirate
using magnetic antibodies against CD133
and CD34. These cells were grown in classic stem cell medium (containing bFGF) and
PRGF medium. We showed that PRGF is a
highly efficient in vitro expansion medium
for EPCs’. Immunostaining and real time RTPCR analysis showed persistence of angiogenic markers on CD34+ and CD133+ but
in a lesser extent on the CD34-/CD133- cells
up to 21 days of culture. In addition, the
capacity to form a cellular network after expansion in PRGF medium indicates that the
EPC-PRGF association could have a positive
influence on the formation of a vascular network within tissue engineered constructs.
Taken together these results suggest a high
potential for the association of PGRF–EPC in
the development of endothelialized autologous bone graft together with MSCs.
Publications: Pres: 15, 84, 85, 88.
Partners: A. Scherberich, Institute for Surgical Research and Hospital Management,
UniversityHospital Basel, Switzerland
Goal 2
Optimizing load and surface motion regimes to stimulate chondrocytes-scaffold
constructs under serum free conditions
Animal or human serum is commonly used
as a supplement for in vitro culture of chondrocytes including cartilage tissue engineering studies. However, due to the avascular
nature of cartilage in vivo, serum is not a
component of the physiological environment of chondrocytes. Addition of serum to
a cell culture system remains an undefined
supplement that can variably influence the
response of cells to biomechanical signals. In
contrast, a serum free culture environment
facilitates investigation of mechanotransduction mechanisms and effects of defined
supplements such as anabolic or catabolic
agents. Using our custom designed bioreactor that mimics the articular motion of joints,
we studied the effect of load and surface
motion on 3-D chondrocytes-polyurethane
constructs, free from influences of serum
components.
Similar to observations with constructs cultured in serum containing medium, one
hour of compression and surface motion applied twice a day significantly up-regulated
the gene expression and release of important cartilage matrix and surface proteins.
In constructs stimulated only once a day,
expression levels were also elevated compared to unloaded controls, although to a
lesser extent than in constructs stimulated
twice a day.
Our data indicate that the response to load
and surface motion is independent of factors present in serum, since the regulation
of gene expression and molecule release is
similar to observations under serum containing conditions. Of particular interest is
the (mechano)-regulation of cartilage matrix and surface molecules. In this respect
our well-defined culture and mechanical
stimulation system provides a powerful tool
for studying mechanotransduction mechanisms or synergistic/antagonistic effects of
biomechanical and biochemical mediators.
Importantly, the frequency of applied loading cycles clearly determined the extent of
response. Both the increases in gene expression and in protein synthesis were stronger when constructs were stimulated twice
a day compared to once a day. This suggests
that repetitive loading may be necessary to
achieve a stronger response. Follow-up experiments will evaluate if shorter intervals
between loading cycles can further enhance
the effect. Optimization of the intervals between loading periods may improve not only
in vitro cartilage tissue engineering but also
in vivo physical therapy strategies.
Publications: Pub: 11, 31; Pres: 65, 66.
Partners: M.A. Wimmer, Rush University
Medical Center, Chicago IL, USA; A. Goessl,
R&D Baxter Biosurgery, Vienna, Austria
Chondrogenesis of human bone marrow
mesenchymal stem cells in fibrin-polyurethane composites
Tissue engineering is believed to be the future of articular cartilage repair because of
the unsatisfying results of the current clinical
procedures. Mesenchymal stem cells derived
from bone marrow (BMSCs) have demonstrated the multipotential to differentiate into
several cell lineages, including chondrocytes.
Stem cells can be harvested relatively easily.
While the procedure causes discomfort to
the patient, it is far less invasive or destructive than articular cartilage harvesting procedures. These advantages have made BMSCs
the alternative cell source to chondrocytes
for articular cartilage tissue engineering. It
is well known that chondrogenic differentiation of BMSCs can be induced in suspension pellet cultures. However, one drawback
with the pellet culture system is that the tiny
BMSCs pellets cannot serve as a template for
neo-tissue formation. Our study found that
chondrogenesis of BMSCs can be induced in
a 3-D fibrin-polyurethane composites system
within chondrogenic medium. Transforming
growth factor ß1, dexamethasone and the
seeding concentration are also factors that
influence the chondrogenic differentiation of
BMSCs. Since the fibrin-polyurethane composites are mechanically stable, this study
has established a basic culture system for
further investigations of the effects of mechanical load on chondrogenesis of BMSCs.
Stable differentiation of human bone
marrow stromal cells into chondrocytes
by transfection with SOX9
Articular cartilage tissue engineering is a
promising treatment for traumatic cartilage injuries, which otherwise do not heal
naturally. In our approach, we use human
mesenchymal stem cells in combination
with SOX9 over-expression and mechanical loading. The final goal is to reach stable
chondrocytic differentiation. The transduced
cells are seeded in a 3-D fibrin-polyurethane
construct and mechanically stimulated.
Cell viability and cell density experiments
were performed. 2, 5 and 10 million cells per
construct proved to be suitable for the experiments in terms of viability and reactivity to
TGF-beta 1. In the 7 days pre-culture period
(no load), the gene expression of collagen-II
and aggrecan increased in the SOX9-transduced samples, while collagen-I was suppressed. This is clearly the beneficial effect of
SOX9 over-expression. Mechanical loading
(surface motion) also had a positive effect
on the expression of another important cartilage marker: PRG4 (lubricin). This protein
lubricates the surface of articulating joints
and has not been shown to be up-regulated
by mechanical stimulation in mesenchymal
stem cells before.
Altogether, our data show that both proper
mechanical loading and SOX9 over-expression positively affect different aspects of
chondrocytic phenotype and that the combination of these two stimuli has a synergistic
effect.
Partners: C.H. Evans, Center for Molecular
Orthopaedics, Brigham and Women’s Hospital, Harvard Medical School, Boston MA,
USA.
Numerical and experimental tissue
engineering
The overall goal of this study is to gather the
information as to how chondrocytes respond
to mechanical stimulation with regard to the
biosynthetic activity. A loading apparatus is
used to apply different regimes of mechanical loading to chondrocyte seeded polyurethane scaffolds and the spatial distribution
of the metabolic activity within the scaffolds
is compared with the spatial distribution of
mechanical values such as strain, fluid pore
pressure and fluid flow velocity. The spatial
distribution of proteoglycan production as a
measure of the metabolic activity is investigated using an autoradiography method (labelling with 35S) which has been established
and optimized (serum containing vs. serum
free medium, 35S concentration, labelling
time, exposure time, image analysis methods and others). A poro-visco-hyperelastic
FE model of the scaffold has been developed
to compute the mechanical parameters. The
investigation of material parameters for a
macro scale continuum model to simulate
the constitutive behaviour of the scaffolds
is currently in progress. A micro scale 3D model based on CT data to investigate
the mechanical state of the environment of
single chondrocytes was set up.
Partners: H. Günther, U.-J. Görke, Chemnitz
University of Technology, Germany; M.A.
Wimmer, Rush University Medical Center,
Chicago IL, USA.
Isolation of committed stem cells
Due to the inefficient methods currently
used to isolate progenitor cells from a sample
of human bone marrow derived cells, a new
approach is needed. At present the cells are
subjected to a simple separation method such
as Ficol gradient followed by attachment to
tissue culture plastic, or antibody based sorting of cell surface markers. As there are no
stem cell specific markers these methods,
rather than producing a pure population of
stem cells, result in an enriched population
of cells. As the population is still very heterogeneous, results obtained can be varied
and unpredictable. The effects caused by the
unwanted cells are unclear and complicate
any experimental model. For these reasons,
we are investigating novel ways of identifying and isolating stem and progenitor cells,
which do not involve the use of cell surface
markers. Using reporter systems that identify
the presence of transcription factors associated with a particular phenotype, it is possible to identify sub-populations of cells of
the desired phenotype. Using this system, it
has been possible to identify a population of
cells which were committed to the osteoblastic phenotype within 55 hours of stimulation. This is significantly faster than the usual
methods, which take 2–3 weeks. The same
method is being further developed to isolate
the identified cells, which should result in a
homogeneous population of cells. This can
be used to more easily identify mechanisms
of differentiation, while also provide the ability to produce a pure population of cells for
tissue engineering purposes.
Phenotype expression of intervertebral
disc cells: Looking for cell specific markers
This study aims to identify a set of marker
genes that may characterize nucleus pulposus (NP) cells of the intervertebral disc (IVD)
and distinguish them from articular cartilage (AC) or IVD annulus fibrosus (AF) cells.
Particularly with regard to stem cell based
NP regeneration strategies, expression of NP
specific genes may become instrumental in
monitoring or triggering stem cell differentiation towards the NP cell phenotype. Moreover, the specific expression of distinct genes
may provide new information about developmental, metabolic, or functional characteristics of IVD cells. Using microarray, quantitative RT-PCR, and immunohistochemistry
techniques, we have described, in the rat,
a set of genes, which may differentiate between NP cells and AF or AC cells. Interspecies and (intra-species) spatial variations
are, however, expected as a result of differences in mechanical requirements and the
development of the NP. To investigate the
potential of certain genes as suitable markers across species, we assessed gene expression levels of beagle dog lumbar and caudal
discs and AC. Furthermore, gene expression
profiles of cells isolated from healthy human
IVD and AC were analysed by microarray.
Our studies demonstrate that observations
from one species can only be translated to
another species after careful consideration.
In addition, the expression of certain molecules may also depend on the age of the tissue and its localization. Thus, although the
relative expression profiles of beagle lumbar
and caudal disc tissues were generally similar, there were differences in the absolute
expression levels that have to be considered.
Nevertheless, certain genes appear to show
consistent expression patterns among different species. As expected, human cells were
found to be more comparable to beagle than
to rat cells. Additional samples from human
individuals of variable age will need to be
analysed comprehensively, including immunohistochemical studies, to be able to elucidate the disc cell specific phenotype(s).
Publications: Pub: 30; Pres: 5, 64, 118
Partners: D. Sakai, J. Mochida, Tokai University School of Medicine, Kanagawa, Japan.
Mechano-Biology Program
Intervertebral Disc
Effect of limited nutrition on intervertebral disc cells under physiological loading
One cause of disc degeneration is limiting
nutrition combined with certain mechanical stimuli. Recently; a novel in vitro system
was developed for culturing whole intervertebral disc (IVD) explants with natural
controlled loading through intact endplates.
In this study, the short-term (7d) response
of disc cells, in their native extra cellular
matrix (ECM), to nutritional challenge and
“physiological” load was investigated. Discs
from Swiss Alpine sheep were cultured for
7d either in media with limited (2 g/l) or sufficient (4.5 g/l) glucose concentration under
“physiological” loading. Cell viability was determined by LIVE/DEAD stain, microscopical
imaging and macro quantification. Relative
gene expression of selected genes was determined by real-time RT-PCR. Glycosaminoglycan (GAG) synthesis rate (CS846 ELISA)
and metalloproteinase activity (zymogram)
were evaluated. In fresh discs, cell viability was ~90% and could be maintained for
at least 7d culture but dropped significantly
to ~57% under limited conditions. RT-PCR
analysis did not reveal any significant differences between d7 sufficient and d7 limited
discs. Although CS846 content did increase
with limited vs. sufficient glucose in the annulus fibrosus, this was not significant. In
the nucleus pulposus, there was a trend for
an increase in CS846 for the limited group.
There was no large difference between
groups using MMP zymography. In this culture system, with media containing “sufficient” concentration of glucose, cell viability
and matrix synthesis at the gene expression
level was maintained up to 7 days in culture. Limiting nutrition increased cell death.
In terms of compensatory mechanisms of
remaining disc cell population, the results
do not provide a clear observation. Matrix
proteins were not up-regulated at the mRNA
level but the synthesis rate of GAGs was increased in the nucleus pulposus. Hence, the
remaining cells tended to increase their GAG
production to compensate for the dead cells.
Increasing cultivation time up to d21 may
allow us to clarify these issues.
Publications: Pres: 4, 63, 79.
Partners: S. Ferguson, MEM Research Center, Institute for Surgical Technology and
Biomechanics, University of Bern, Switzerland
The Fate of injected Bone Marrow Derived Stem Cells into Bovine Caudal
Intervertebral Discs
Bone marrow-derived stem cell (BMSC)
injection can retard disc degeneration and
that matrix production is also dependent on
BMSC:nucleus pulposus cell (NPC) ratios.
Here we use our previously established in
vitro culture system of whole disc organ culture to investigate regenerative properties of
BMSCs in a disc with reduced cell number
and cellular activity. Bovine caudal intervertebral discs (IVDs) with adjacent bony
endplates were harvested and fresh frozen
in liquid N2 in cryo-protectant (10% DMSO,
10% glycerol and 10% fetal calf serum in
DMEM) to produce discs with 50% endogenous cell viability. After one week of freezing, discs were thawed and cultured under
physiological mechanical loading for seven
days. Remaining endogenous disc cells survived during the seven days culture. Bovine
BMSCs were labelled with red fluorescent
membrane dye (PKH-26), embedded in a
peptide hydrogel and injected into nucleus
pulposus of IVDs. Cell Viability of BMSCs
determined semi-quantitatively using live
cell stain (Calcein AM green) and blue nucleus stain (DAPI) using confocal laser scanning imaging dropped significantly already
at day 0 to ~60%, over seven days culture
it dropped even further to ~25%. However,
qualitatively, BMSCs showed adaptation in
disc environment, where injected cells were
spread out and started to attach to disc matrix. However, anabolic genes (i.e. aggrecan,
collagen I, collagen II,) expression, compared
between day 0 and day 7 for injected and
endogenous cells combined, tended to be
downregulated in expression while catabolic
genes (i.e. ADAMTS-4 and MMP-13) were
increased about 10 times. Histological staining showed that the freeze-thaw processed
discs had preserved an organized extracellular matrix (ECM) and disc structure with
elliptic chondrocytes in endplate (EP), dense
fibrous connective tissue in the inner and
outer annulus fibrosus at day 0. However,
ECM was significantly lost in nucleus pulposus after 7 days.
This ex vivo model allows study of BMSC18 | Activity Report 2007
NPC interactions, and how BMSCs may be
used to delay disc degeneration. Moreover,
effects of nutrition and loading on BMSCNPC interactions in the native organ will be
further investigated. Furthermore, it will be
investigated if cell survival may be considerably improved by preconditioning of BMSCs
in coculture with NPC.
Publications: Pres: 55, 63.
Partners: K.M.C. Cheung, University of
Hong Kong, HK.
Regeneration of the intervertebral disc by
strain modulation and growth factors
Initial experiments in our laboratory supported the hypothesis that controlled intervertebral compression may stimulate the regeneration of a cartilaginous tissue following
nuclectomy in a rat-tail model. Furthermore,
recent in vitro studies have demonstrated
that hydrostatic pressure alone or combined
with TGF-ß influences differentiation and
matrix synthesis of mesenchymal stem cells
(MSCs) making them promising candidates
for cell-based therapies for disc repair and
regeneration.
For this purpose, MSC are often cultured in
a 3D hydrogel matrix (e.g. alginate and agarose), which is strong enough to be loaded
and which has been widely used for articular chondrocytes (AC) and nucleus pulposus
(NP) cells. However, we could demonstrate
that in contrast to ACs and NP cells from
the same animal, only a small fraction of the
initially seeded undifferentiated BMSC could
thrive in the same hydrogels under the same
conditions. Since cell number and hence cell
survival is a key factor for tissue regeneration, cell survival of BMSC within hydrogels
should be improved. We are currently investigating if pre-conditioning of BMSCs by
induction of chondrogenesis as well as mechanical stimulation in long-term cultures
may be a worthwhile strategy.
Partners: Biomaterials and Tissue Engineering Program; M. Aebi, MEM Research Center, Institute for Evaluative Research in Orthopaedics, University of Bern, Switzerland.
In vivo ovine model of vertebral endplate
perfusion insufficiency
The cells inside of the intervertebral disc
depend on diffusion for their nutrition and
disposal of waste products. It has been hypothesized that a decrease in the diffusion
rate could be a cause of IVD degeneration. In
this project, an ovine model for solute transport insufficiency induced disc degeneration
is being developed to study the pathogenic
mechanism and its treatment.
An acute study showed that a perfusion
block of the intervertebral endplate resulted
in diffusion inhibition of N2O into the nucleus pulposus of the intervertebral disc. In a
short term study, this showed to be difficult
to repeat. 2 weeks after the initial placement
of the perfusion blocks only 4 out of the 14
‘blocked’ discs showed and diffusion inhibition, and also a drop in cell viability. This
could be an effect of recovery of the blood
supply, or bad placement of the perfusion
blocks.
In an extra experiment in which diffusion
was measured during the first surgery (like
in the acute study) and during the second
study (as in the short term study), this issue has been resolved. The perfusion blocks
were placed very closely to the endplate and
during the first and second surgery the diffusion was inhibited, ruling out recovery. The
placement was just not close enough.
A new set of experiments have been planned
in which close attention will be paid to the
placements of the perfusion blocks. Furthermore, the study duration will be 4 weeks
instead of 2 to see greater effects of this perfusion block on the cellular behaviour.
Publications: Pub: 46; Pres: 148.
Partners: C.C. van Donkelaar, Eindhoven
University of Technology, NL.
Bone Healing
Mechanoregulation of BMSC differentiation in an uniaxial compression bioreactor
Due to their high proliferative rate and
multipotentiality, mesenchymal stem cells
(MSCs) have been proposed as a source of
regenerative cells for numerous tissues, including bone and cartilage. It has long been
recognized that MSC proliferation and differentiation are regulated by biological and
biophysical factors, but recent experiment
suggested that they could also be regulated
by their mechanical environment. Although
theoretical models have been developed to
relate mechanical loading to skeletal tissue
differentiation, it is not clear how valid are
these models for the establishment of loading regimes favouring osteogenic and chondrogenic MSC differentiation in a bioreactor. This project address whether proposed
mechanoregulation algorithms are valid for
in vitro differentiation of MSC.
The goal of the project can only be achieved
if the local physical stimuli applied to the
cells are known as a function of the external loads applied on the construct within
the bioreactor. Finite element analysis of
the cell carrier was chosen to calculate these
local conditions, but requires an accurate
constitutive model of the carrier material.
The poroviscoelastic finite element model
previously developed for fibrin scaffolds was
validated for a particular composition by using a hybrid method that combined stress
relaxation experiments under unconfined
compression, analytical analysis of the poroviscoelastic equation, and numerical optimization. Moreover, a new experimental
protocol including image analysis has been
designed to track the transient radial expansion of the fibrin specimens during the test,
and to force the optimization procedure to
give unique poroviscoelastic parameters.
The design of the bioreactor developed for the
early mechanotransduction assays was also
updated and optimized to obtain more accurate measurements and better statistics. The
new built bioreactor consists in four loading
units working under displacement control at
16 bits with a resolution 1µm. Each load unit
is able to load similarly 6 constructs placed
in 6-well plates that can be easily removed
for medium change under sterile conditions.
Mechanical stimulation of the fibrin scaffolds
is afforded through a low mass-inertia system activated by a pneumatic actuator.
From the biological side, fibrin carriers seeded with rat MSCs were loaded at 2, 5, and
10% strain for 7 and 14 days. The compressive loads, however, did not lead to well
characterised differentiation patterns, even
after 14 days of stimulation. Those results
are partially explained by low survival of rat
MSCs inside fibrin carriers. Different conditions of fibrin synthesis (fibrinogen, thrombin, calcium, chloride, and factor XIII concentrations) have then been tested to find
a formulation in which cell can survive and
spread and that can be mechanically characterized and stimulated. This formulation
will be now tested in the new bioreactor and
effects on mechanical stimulations on MSC
differentiation will be assessed.
Partners: H. Van Oosterwyck, Catholic University of Leuven, Belgium; T. M. Quinn,
McGill University, Montreal, Canada; W.
Wilson, K. Ito, Eindhoven University of
Technology, NL
Computational cell based mechano-regulation model of tissue differentiation
during fracture healing
To improve fracture treatment, a better understanding of mechano-regulation mechanism at the cell and tissue level is important.
Previous projects led us to believe more accurate computational description of cellular
processes is necessary to achieve corroboration. We hypothesize that by improving
computational description of cellular processes, an algorithm regulated by deviatoric
strain and fluid flow can be fully corroborated in vivo results.
A computational model including detailed
modeling of cell parameters has been developed using finite element analysis (software
ABAQUS). The cell equation contains separate parts describing proliferation, differentiation, apoptosis and transport due to migration of cells, as well as matrix production
and degradation. All parameters are depending on cell phenotype, concentration and
local mechanical stimulation. Cell specific
parameters from literature have been implemented to describe mesenchymal stem cells,
fibroblasts, chondrocytes and osteoblasts,
fibrous tissue, cartilage and bone. The model successfully predicted the normal bone
fracture repair processes, as well as alterations due to mechanical overloading. It also
predicted known alterations due to changes
in the biological environment, such as periosteal stripping and impaired endochondral
ossification. Statistical methods were used
to evaluate the importance of each cellular
parameter and it was shown that most important parameters during bone healing are
those related to cartilage formation and replacement. This also corresponds well with
what is believed to be important experimentally and clinically.
To explain the peculiarities during the remodelling phase of fracture healing in mice,
a well known bone remodelling algorithm
was adopted. Various mechanical loading
protocols were evaluated and it was shown
that a high degree of bending on a mice
femur, compared to human femur, can explain the formation of dual cortices observed
during the remodelling phase of healing.
Publications: Pub: 22; Pres: 72, 73, 74.
Partners: K. Ito, R. Huiskes, C.C. van Donkelaar, Department of Biomedical Engineering,
Eindhoven University of Technology, NL
Fixation compliance in a mouse fracture
model induces two different processes
of fracture healing but does not lead to
delayed union
Delayed unions are a problematic complication of fracture healing whose pathophysiology is not well understood. Currently,
they can only be diagnosed when already
well developed. The standard treatment is a
secondary operative procedure. In order to
identify potential molecular targets diagnosis
and treatment of delayed unions, a potential
in vivo murine delayed union model was
investigated. In humans, fixation flexibility
and gap size are two factors associated with
delayed unions. In this study, it was investigated whether this was similar in mice. For
this purpose, two internal fixators, one with
a ¼ the bending stiffness of the other, as well
as special surgical instruments, were developed for the mouse femur. µCT, radiographs,
4pt-bending tests and histological analysis
demonstrated that the different fixator types
led to two different healing pathways. The
bridging plate induced only intramembranous ossification whereas the more flexible
bridging plate induced a mixture of endochondral and intramembranous ossification.
However, the different fixator types led to a
delay in healing of only 3 to 5 days in the period between 14 and 21 post-operative days.
In mice, considerable fixation flexibility is
necessary to induce secondary fracture healing similar to that which occurs in humans,
but that it is not sufficient to induce a substantial delay healing.
Partners: R. Matthys-Mark, AO Development Institute, Davos, Switzerland.
Fracture Treatment
Hydroxyapatite particles to improve
implant osseointegration in osteoporotic
trabecular bone
In osteoporotic bone, remodeling is altered,
whereby bone resorption exceeds bone formation and consequently bone volume and
bone contact decreases in the peri-implant
region. As a result, implant loosening and/
or failure may occur. Current approaches
to reduce the effect of remodelling on secondary implant stability are based on pharmaceutical methods (e.g. bisphosphonates,
parathyroid hormones). The objective of this
study was to determine if a simple alternative based on the integration of non-resorbable osteoconductive hydroxyapatite (HA)
particles (Endobon) could also preserve the
bone mantle around a screw implant. We
hypothesized that implanting such particles
in the peri-implant region in an osteoporotic
rat model could maintain a more dense and
functional peri-implant bone structure, by
shifting remodeling events.
Adult female Wistar rats were ovariectomized and after 4 weeks their osteoporotic
state was verified with in vivo bone mineral density (BMD) measurements using an
XtremeCT®. Titanium screws were implanted bilaterally into the proximal tibial metaphysis. In the right tibia, the drill-hole was
filled with 6 mg of HA particles before screw
insertion. The rats were euthanized at different time points to investigate the changes in
the peri-implant region over time. The explanted proximal tibiae were scanned with a
μCT40® at a resolution of 16 m and analyzed
with a custom image processing macro to
filter out screw and HA artifacts. In 8/12
tibiae of each time point, histomorphometric
analysis was performed using conventional
staining protocols to quantify lamellar and
woven bone area percentage as well as to
monitor cellular activity around the screw
in the mid-sagittal section. The remaining
4/12 animals underwent mechanical pullout testing.
The microCT results showed that there was
a significant change in peri-implant bone
volume density (BV/TV) over time. BV/TV
was significantly higher in the HA- over the
control-side at all time-points. No correlation was detected between the pull-out force
and the volume of peri-implant bone. Better correlations resulted between pull-out
force and mean bone matrix mineral density. Results from the histological analysis
demonstrated that lamellar bone area percentage significantly increased with time on
both sides. After a similar initial abundant
increase in woven bone area, woven bone
was subsequently resorbed differently, remaining significantly higher on the HA-side
compared to the control-side. These results
indicate that HA particles inhibit resorption
of woven bone without affecting lamellar
bone growth, thus resulting in maintenance
of a denser peri-implant bone mantel.
Partners: R. Matthys-Mark, AO Development Institute, Davos, Switzerland; R. Müller, Institute for Biomedical Engineering,
Swiss Federal Institute of Technology ETH,
Zurich, Switzerland.
The role of periosteal injury for development of delayed unions in an in vivo
murine model
Delayed unions remain an unresolved clinical issue and its pathogenesis is poorly understood. Many etiologies are suspected of
which the perisoteum may play a key role.
The periosteum is important for bone perfusion and it is a source of progenitor cells during fracture healing. Hence, periosteal injury
may lead to impaired healing. In this study,
we investigated the effect of a standardized
periosteal injury on healing of a gap osteotomy in a mouse model.
Using C57BL6 mice, a 0.45 mm femoral middiaphyseal gap osteotomy was stabilized by
a MouseFix™ plate with loosened screws
to promote indirect healing. In half of the
mice, the periosteum adjacent to the gap
was injured by standardized cautery. Mice
were euthanized at different time points between 1 and 42 days. Micro-CT analysis was
performed to quantitatively determine the
amount of woven and lamellar bone around
the fracture gap. Femora with 21, 28 and 42
days of healing were tested in 4-pt. bending.
Histomorphometry and immunohistochemistry are currently carried out on mid-sagittal paraffin sections.
The micro-CT evaluation showed a significant effect of periosteal injury on callus
growth. Both with and without periosteal
injury, the amount of woven bone started
to increase at day 7 and reached a peak
around day 21, but the injury suppressed
callus growth resulting in less woven bone.
Resorption of woven bone started around
day 21, and at day 42 there was less woven
bone in the group without injury. Lamellar
bone volumes did not change much during
healing and did not differ between groups.
Stiffness was significantly lower for the periosteal injury group at each time point. After
21 to 28 days of healing, the mean stiffness
of all osteotomized femora was 32% and
42% of contralateral intact femora for the
samples with and without periosteal injury,
respectively. After 42 days the stiffness increased significantly to 54% and 68%, respectively.
In conclusion (with the histological results
still pending) the periosteal injury applied in
this mouse model seems to affect the course
of bone healing. The growth of new bone
in the callus was inhibited resulting in less
functional capacity (stiffness) at similar healing duration. This delay was also confirmed
by (clinical more relevant) radiographical
scores. However, this functionality continued to improve with time similar to without
injury and appears that it will recover completely at a later time point. A more precise
analysis of the micro-CT data by separating sub-regions of interest (i.e. within gap,
between cortices and periosteal/ endosteal
side) as well as the histological evaluation
will provide more data regarding healing
pattern and distribution of different tissues.
Partners: R. Matthys-Mark, AO Development Institute, Davos, Switzerland.
Bioperformance of Mate-
Goal 1
Publications: Pres: 6, 8, 69, 70, 71.
Partners: C.W. Archer, Cardiff University,
Wales, Great Britain; Synthes Inc., Paoli PA,
USA.
Group: Interface Biology
Effect of implant surface microtopography and material type on osteoblast
cytocompatibility and differentiation
Effect of surface topography on removal
of cortical bone screws in a novel sheep
model
For long term implants such as spine cages
& hip prostheses, the need for osseointegration is indisputable. In paediatric fixation,
where the majority of implant removals occur, complications relating to excessive bony
overgrowth account for approximately 13%
of all difficulties encountered. Surface mi-
Difficulty in removing fracture fixation implants is a complication seen frequently in
paediatric patients, yet also in adults. It is
believed that increased bone adhesion to
these implants is a major contributing factor
to this problem. Our in vitro studies have
shown that the surface morphology of im-
rials and Devices Program
crotopography is the major determinant of
bony integration for current clinically used
metals. This study assess in vitro, the potential of surface polishing of the clinically available materials commercially pure titanium,
titanium-6%aluminium-7%niobium (TAN),
and titanium-15%molybdenum (Ti15Mo)
for alleviating excessive bony overgrowth.
Clinically available ‘standard’ micro-rough
samples of each material were included as
positive controls for osseointegration while
electropolished stainless steel was used as
the negative control. Samples were either
electro- or paste polished. Extensive surface analysis was performed of numerous
tests to achieve well polished samples. Our
results show that polishing reduces surface
microdiscontinuities that can be ‘seen’ by
the cells which thereby reduce expression
and function of genes specific for osteoblast
differentiation and maturation, compared
to standard micro-rough counterparts. This
surface induced cell behaviour change is
achieved initially due to the surface altering
the cell shape/cytoskeletal organisation. We
have observed that on polished surfaces, the
frequency of focal adhesion sites amplified
as well as presenting a larger, more flattened
phenotype compared to the typical cuboidal
phenotype attributed to osteoblasts observed
on standard micro-rough surfaces. These reductions in gene expression were not due
to decreased cell numbers, or differences in
rates of proliferation on polished samples, as
these parameters were found to be similar.
We suggest that surface polishing is an effective & simple method for reducing excessive
bony overgrowth by altering osteoblast cell
shape and therefore cellular function.
plant materials has the ability to influence
cellular responses with polished surfaces
decreasing the potential for mineralisation.
This study examined the effect of polishing of two clinically used materials, titanium
and the titanium alloy TAN, on the torque
required to remove screw type implants and
on the percentage bone-implant contact in
both cancellous and cortical bone simultaneously over three time periods of 6, 12
and 18 weeks. It was found that polishing
had a significant effect on both removal
torque and percentage bone-implant contact in cancellous and cortical bone, with
the polished implants demonstrating a lower
removal torque in both cortical and cancellous bone. Polished titanium and stainless
steel were similar in terms of surface roughness and removal torque however; polished
TAN, which was not as smooth as polished
titanium did not show the same potential for
reducing removal torque. The results of the
study show that polishing is promising in
improving the ease of implant removal after
fracture fixation and repair.
standard micro-rough counterparts. However, the magnitude of the influence of polishing for screws for the locked system was not
as great as noted for cortical screws without
plates in our previous work. This was due
to difficulties with polishing of the smaller
screws. Polishing of the plates was successful
and repeatable. In longest term implantation
of 18 months polishing eased tissue removal
(both soft and bone) enabling exposure of
plates and screw heads within 3–5 minutes
compared to 20 minutes (or more) for the
standard micro-rough plates. This ease of tissue removal will save time and surgery costs
and reduce the clinical problems during removal of the plates and screws in temporary
fixation.
Publications: Pres: 90, 99, 109, 114, 115.
Wales Great Britain; Synthes Inc., Paoli PA,
USA
Fractures of the tibial and femoral diaphysis
are commonly repaired by intra-medullary
(IM) nailing. Currently IM nails are available as electropolished stainless steel (EPSS)
or as a titanium alloy such as Titanium-Aluminium-Niobium (TAN), which has overall better mechanical and biocompatibility
properties than steel. After fracture healing,
nail removal is common, though often has
complications with TAN, as opposed to EPSS
of the same design. We propose that the
exceptional ability of TAN to promote strong
bone on-growth as a main reason. In vitro
work in our group has shown that smooth
TAN surfaces cause a loss of osteoblastic phenotype like behaviour. In vivo work in our
group has shown that polishing of TAN cortical screws significantly reduced the removal torque required for both trabecular and
cortical sheep bone. In this study, we are assessed the effect of polishing of TAN IM nails
on direct bone contact, and extraction force
after 12 months implantation in sheep tibia
medullary canals. The pullout results demonstrate that the surface microtopography of
the IM nails has a significant effect upon the
force required to remove the nails. Both the
EPSS nails and the polished TAN nails were
significantly easier to remove than the standard microrough TAN nails. Observations of
the surfaces of the polished TAN nails after
removal showed no bone adhesion to the
The effect of surface treatment of lockedscrew and plate combinations on boneimplant adhesion and implant removal in
a sheep model
Fracture fixation implants that require removal such as locking plate / screw combinations can be difficult to extract due to
excessive bony ongrowth. This can increase
surgical time and associated costs, as well as
the chances of debris contamination, blood
loss and patient trauma. Our previous in
vitro and in vivo studies highlighted surface
topography as the major determining factor
for tissue integration of titanium and titanium alloy implants and that surface polishing alleviates excessive bony overgrowth for
ease of device removal. The aim of this study
was to assess the effect of surface polishing
of locking plate / screw devices on the screw
removal extraction torque required, as well
as on tissue / screw integration after 6, 12
and 18 months implantation in sheep tibial
cortical bone. The extraction torque results
show lower values for polished screws than
Partners: Synthes Inc., Paoli PA, USA
In vivo evaluation of the effect of surface
treatment of TAN intramedullary nails
upon nail removal
surfaces. Bone within the nail interlocking
holes also did not grow directly onto the
polished surfaces and was easily pushed out
with a K wire. Histomorphometric analyses
to assess bone contact are pending. Our results show that surface polishing of IM nails
and interlocking screws will greatly help the
surgeon.
Nanobiomimetics for bone tissue engineering: measuring how topography
influences primary osteoblast adhesion
and differentiation
Polymeric medical devices are widely used
in orthopaedic surgery and play a key role in
fracture fixation and in areas of orthopaedic
implant design. Topographical modification
and surface micro-roughness of these devices regulate cellular adhesion, a process
fundamental in the initiation of osteoinduction and osteogenesis. Advances in fabrication techniques have evolved the field
of surface modification and, in particular,
nanotechnology has allowed the development of experimental nanoscale substrates
for the investigation into cell-nanofeature
interactions.
This study was established to investigate
the effects of nanoscale topography on human osteoblast (HOB) adhesion and mesenchymal stem cell (MSC) differentiation.
Adhesion subtypes in HOBs were quantified by immunofluorescent microscopy and
adhesion formation investigated via immunocytochemistry with scanning electron microscopy and also green fluorescent protein
live cell imaging. To investigate the effects of
these substrates on cellular function 1.7 k microarray analysis was used to establish gene
regulation profiles of enriched MSC populations cultured on these nanotopographies.
Nanotopography differentially affected the
formation of adhesions on experimental
substrates. Planar controls induced adhesion formation. Nanolacuni and nanoislands
reduced adhesion formation, yet increased
cellular spreading; nanopits however were
shown to inhibit directly the formation of
large adhesion complexes. MSCs cultured on
experimental substrates revealed significant
changes in genetic expression. This included
down-regulation of canonical signalling and
functional pathways on electron beam li24 | Activity Report 2007
thography substrates, whilst the same pathways were upregulated on nanoislands and
nanolacuni substrates. This study implicates
nanotopographical modification as a significant modulator of osteoblast adhesion and
cellular function in mesenchymal populations.
Publications: Pub: 3, 4; Pres: 40, 41.
Partners: M. Dalby, C. Wilkinson, Glasgow
University, Great Britain.
Investigation of the behaviour of cells
derived from soft and hard tissues on
surface modified PEEK for internal fracture fixation
Evaluation by X-ray of post-operative intervertebral body fusion can be obscured by the
presence of metal devices. MRI examination
of metal devices can also lead to artefacts.
Therefore some spine cages and CMF implants have been redesigned in a polymeric
material, Polyetheretherketone (PEEK).
PEEK is radiolucent, allowing visualisation
of the tissue-implant interaction and its mechanical properties can be tailored to closely
resemble those in the region of implantation. However, PEEK has low surface energy, which can lead to fibrous encapsulation.
Through surface modification the surface
energy can be increased to aid adsorption
and attachment of proteins and cells. The
in vitro characterisation of the interaction
of cells derived from soft and hard tissues
with surface chemistry modified PEEK is being investigated. The effect of the surface
treatment on the chemistry and topography
was characterised by XPS, contact angle and
AFM. The modified PEEK surfaces were
shown to have an increase in surface oxygen,
improved wettability and minimal change in
the surface topography. In vitro experiments
have shown primary human osteoblast-like
(HOB) cells to attach and proliferate more
readily on the surface modified PEEK and
SEM has shown the cells form monolayers
similar to those on titanium surfaces. Alizarin red staining of calcium showed the HOB
cells have formed nodules on the modified
PEEK surfaces. We anticipate that an optimised PEEK surface will, in comparison to
unmodified PEEK, enhance cell adhesion
and function, thereby leading to improved
PEEK implant tissue integration.
Partners: Invibio Ltd., Thornton Cleveleys,
Great Britain; Synthes Inc., Paoli PA, USA
The effect of serum free medium and
culture chamber design on osteocyte viability of ex-vivo cultured human cancellous bone cores
In order to overcome internal experimental
variability seen while culturing human cancellous bone explants under cyclical loading
conditions, a serum free (SF) medium was
created. TGF-ß3 was added to SF-medium,
as our previous experiments demonstrated
that the growth factor maintains higher osteocyte viability during bone explant culture
with serum containing medium. Quantification of viable osteocytes was performed.
Human femoral heads from osteoarthritic
hip replacement patients were processed to
5x10mm cancellous bone cores. These cores
were cultured, and loaded daily for 14 days
with the use of the Zetos bioreactor. Using
the lactate dehydrogenase viability staining
method developed within our group the use
of DMEM serum free (SF-DMEM) + 15 ng/ml
TGF-ß3 showed in most cases a comparable osteocyte survival in the centre of long
term cultured cores compared to the use of
DMEM + 10% FCS. The response of osteocytes to the applied growth factor is dependent on the cellular presence of its receptors.
TGF-ß receptor I and II were investigated
immunohistochemically after long term
culture in SF-medium containing TGF-ß3.
Whereas receptor I could be found on osteocytes and their canaliculi, receptor II was
detected more rarely and predominantly on
bone-lining cells. Bone matrix synthesis of
the explant cells during long term culture
was analysed immunohistochemically. Bone
cores cultured in serum containing DMEM,
as well as cores in SF-DMEM + TGF-ß3, labelled positive for the C-terminal propeptide
of type I collagen. An additional positive effect with the use of SF-medium was the reduction of unwanted surface fibrous tissue,
observed during culture in FCS containing
medium. This tissue reduces nutrient availability for the bone explants and could secret
factors that affect the culture. The SF-medium ensures more defined culture conditions.
Within the ESA (European Space Agency)
microgravity application programme, which
funds this work, an unmanned ESA Space
Flight Experiment ‘foton M3 mission’ was
sent to space in September. We investigate
the responses of cultured, daily loaded bovine cancellous bone explants at zero gravity
compared to normal gravity. We are currently analysing the cultured cores by µCT
and histology.
Publications: Pub: 37; Pres: 11, 12, 77, 78,
95, 96.
Wales, Great Britain; J. Van der Sloten,
Leuven University, Belgium; D.B. Jones,
Philipps University, Marburg, Germany.
Goal 2
Influence of material and microtopography on the development of local infection in vivo
Polishing the surface of fracture fixation implant materials alters fibroblast & osteoblast
behaviour in vitro and reduces soft tissue
adhesion & bony overgrowth in vivo. Thus,
surface polishing may decrease complications and ease implant removal. Surface polishing may also influence the susceptibility
of an implant to bacterial colonization. This,
however, remains unknown and needs to be
ascertained. In this study, the local infection
rate associated with clinically available titanium (Ti) ISO 5832/2 and titanium aluminium niobium (TAN) ISO 5832/11 in their
standard microrough form is compared with
that of their test polished equivalents and
also to clinically available electropolished
stainless steel (EPSS) ISO 5832/1. Locking
compression plates (LCP’s) of each material and topography were implanted onto
the tibia of New Zealand White rabbits and
inoculated with bacteria immediately upon
wound closure. The bacterial inoculum was
sequentially adjusted after each experimental phase towards the intended ID50 (bacterial concentration causing a 50% infection
rate) at which the differences in infection
rates is most evident. Five separate phases
have been completed to date and the final
phases will be completed in early 2008. The
preliminary data has shown that polished
TAN plates display the greatest resistance to
infection, followed by standard TAN (both
requiring 107 bacteria for ID50), followed
by polished Titanium, EPSS and finally stan-
dard Titanium (all requiring 106 bacteria for
ID50). Definitive, statistically significant results will only be available upon completion
of the study. Our previous in vitro results
showed a significant decrease in the amount
of bacteria adhering to polished TAN compared to standard TAN surfaces and we did
not detect a difference between polished and
standard titanium.
Publications: Pub: 18.
Histology/ Imaging / Service
Regional distribution of cancellous bone
in osteoporotic and non-osteoporotic
distal radii
The distal radius fracture is the most frequent fracture in adult patients (17.5% of all
fractures) and 45.8% of all patients suffering
from distal radius fractures are older than
65 years. The objective of this investigation
was to determine whether there is a homogeneous manifestation of osteoporotic bone
density decrease in all regions of the distal
radius. Twelve fresh frozen distal radii were
included. The bone quality was assessed using standardized clinical qCT measurements
and the radii were divided into two groups
(good and bad bone quality). VivaCT measurements were obtained at a resolution of
39µm in varying distance from the radiocarpal joint surface. The resulting radiological
cross-sections were divided into 4 quadrants
and the cancellous bone density (area bone
/ ROI) was histomorphometrically assessed
in each of them. To define the 4 quadrants
the center of gravity was determined for
each cross-section. The histomorphometrical measurements (bone volume (BV) /
total volume (TV)) were obtained using a
Zeiss KS400 image analysis system. In both
groups regional cancellous bone density was
highest immediately beneath the joint surface and decreased towards the metaphyseal
region. There was no statistical difference
between the dorsal and palmar or the radial
and ulnar quadrants of the radius. Comparison between both groups revealed that there
were significant differences in bone density
between them which were least pronounced
directly beneath the joint surface. The study
clearly shows that there is a characteristic
regional distribution of bone density in the
distal radius in normal and osteoporotic patients. In osteoporotic bone density decrease
occurs not homogeneously in all regions and
is least pronounced beneath the joint surface. The results of the present study are in
line with current knowledge that the most
useful position for implant screw fixation
is located directly beneath the joint surface
especially in patients with osteoporosis.
Partners: S. Duda, R. Arora, M. Lutz, Unfallchirurgie und Sporttraumatologie, Medical University of Innsbruck, Austria
Group: Tissue Morphology
Detection of bone graft failure in lumbar
spondylodesis: A matter of spatial resolution as demonstrated by XtremeCT
The objective was to compare the diagnostic
outcome of anterior spondylodesis based on
three different radiological procedures (64line MS-CT, XtremeCT, contact radiographs).
Monosegmental lumbar spondylodesis was
performed in seven sheep using autologous
iliac crest graft or solvent preserved bovine
cancellous bone. The fused spinal segments
were explanted after 12 weeks and examined with a 64-slice-CT, with an XtremeCT
and by contact radiography. In 2D-views,
the area of the disk space bridged by bone
was assessed and the grafts examined for
fractures. In 3 out of 7 cases conventional
clinical CT erroneously showed stable consolidation whereas contact radiography revealed a clearly visible graft fracture. Xtreme
CT likewise revealed the graft fracture in
these cases. There was a statistically significant difference (p=0.038) between the values for bone consolidation of the intervertebral space as observed on conventional CT
and contact radiographs. There also was an
almost significant difference (p=0.053) between XtremeCT and conventional CT in the
present study. The results show that Xtreme
CT, a device which is approved for clinical use, offers a higher resolution of bone
structures than clinical CT. Our results demonstrate that XtremeCT resolution leads to
more correct diagnoses. However, the specimen size limit prohibits the in vivo use of
this method in the human spine. In clinical
practise our results suggest that persisting
symptoms despite radiologically consolidated spondylodesis in some cases may be re-
lated to graft failure which so far cannot be
detected with clinically available methods.
Partners: P.C. Strohm, D. Kubosch, T.A.
Bley, N.P. Südkamp, Department of Orthopaedic and Trauma Surgery and Department for Diagnostic Radiology, University of
Freiburg Medical Center, Germany
Using the fulcrum axis improves the significance of true anterior-posterior x-rays:
A prospective study
The study was designed to improve evaluation of true anterior-posterior x-rays, when
a free visible joint space and a small glenoid
area are essential. The aim of this prospective study was to compare the quality of true
anterior-posterior X-rays obtained either by
conventional or by a newly developed technique. To date, for true anterior-posterior
X-rays the positioning of the patient is defined by turning the body axis of the patient
about 45° oblique towards the film. This often results in an overlapping of the humeral
head and the glenoid (low quality). The axis
between the anterior tip of the coracoid and
the posterolateral acromion angle (fulcrum
axis) is approximately in parallel to the glenoid joint plane. Hence, the positioning of
patients according to the fulcrum axis might
allow for improved quality of true anteriorposterior shoulder X-rays. 200 patients requiring shoulder X-rays were enrolled. In
group I 100 consecutive true anterior-posterior images were obtained using conventional positioning of the patients whereas
in group II 100 consecutive patients were
positioned using the fulcrum axis. For quantitative quality comparison, the amount of
images with free visible joint spaces and the
comparable glenoid size (CGS=ratio between
glenoid height and visible glenoid area) were
analyzed by 3 experienced orthopedic surgeons blinded for the technique for interobserver reliability and repeated 8 weeks later
for intraobserver reliability. The learning
curves of both x-ray techniques were analyzed. The number of complete free visible
glenoid space was significantly higher using
the fulcrum axis (31 vs. 64) and the CGS
increased significantly (0.08 vs. 0.15). The
intra- and interobserver reliability showed a
high consistency for all measurements. The
learning curves of both x-ray techniques ac27 | Activity Report 2007
corded to a horizontal line. Our newly developed patient positioning technique allows
for significantly improved true anterior-posterior X-ray imaging of shoulder joints. The
technique generates constant results from
the beginning and is now ready to use for a
broad application in clinical routine.
Publications: Pres: 45, 48.
Partners: P. Biberthaler, W. Mutschler, Department of Traumatology and Orthopedic
Surgery, Ludwig-Maximilians-University; E.
Wiedemann, OCM-Clinic, Munich, Germany
Long-term reaction to bone cement in
osteoporotic bone: New bone formation
in vertebral bodies after vertebroplasty
This work aimed to gain first insights into the
long-term reaction of bone surrounding the
cement injected into osteoporotic cancellous
bone in human individuals suffering from
osteoporotic vertebral fractures. Vertebral
bodies of a thoracic spine were explanted 3.5
years after vertebroplasty with polymethylmethacrylate (PMMA). The treatment had
been performed due to osteoporotic compression fractures. Individual vertebral bodies were cut in sections after embedding.
The sections were analyzed using contact
radiography and staining with Toluidin blue.
Furthermore pieces were trimmed for evaluation with scanning electron microscopy
and micro-CT. Large amounts of newly built
callus were detected in the surrounding of
the PMMA with all imaging techniques. The
callus formation almost completely filled
the spaces between the vertebral endplate,
canellous bone, and injected PMMA. In trabecular bone former microfractures and osteoclast lacuna were refilled and/or bridged
with newly formed bone. Nevertheless, the
majority of the callus formation was found
in the immediate vicinity of the PMMA
without any obvious relation to trabecular
bone fractures. The results indicate that contrary to the established knowledge even in
osteoporosis the formation of large amounts
of new bone is possible.
Partners: V. Braunstein, Department of
Traumatology and Orthopedic Surgery,
Ludwig-Maximilians-University Munich,
Germany; L. Benneker, P.Heini, Department
of Orthopedic Surgery, Inselspital, University of Bern, Switzerland; K. Yen, Institute
of Forensic Medicine, Medical University
of Graz, Austria; A Gisep, AO Development
Institute, Davos, Switzerland
Metallurgical evaluation of a 316L cast
steel implant from dogs with malignant
tumors and from non affected controls
animals
We wished to investigate the material properties of retrieved plates from dogs with malignoma and to compare them to retrieved
plates from dogs without signs of irritation.
We further wanted to investigate the tissue around the retrieved plates with respect
to presence or absence of particulate debris
and type of tissue reaction. 7 retrieved TPLO
plates from malignoma cases, 7 retrieved
TPLO plates from cases without malignoma
were looked at. Metallurgic analyses was
performed. Tissue samples were obtained
from regions adjacent to retrieved plates and
used for histologic examination. Preliminary results show all TPLO plates exhibited a
2-phase microstructure consisting of austenite and ferrite in various amounts. Residua,
inclusions, and cavities were seen during
microscopic and SEM examination of the
plate surface. The results to date confirmed
that retrieved TPLO plates were manufactured from 316L stainless steel and that not
all plates investigated met the specifications
for material composition of cast surgical implants
Partners: RJ Boudrieau, RJ McCarthy, JH
Keating, Cummings School of Veterinary
Medicine, Tufts University, North Grafton
MA, USA
Contract Research & Support Program
Tissue engineering approaches to repair
a critical size sheep bone defect
Bone loss in the diaphysis secondary to open
fractures, infection, and tumors is a major
clinical difficulty at the present time. Current clinical options including autografts,
and allografts are limited in supply, and have
high complication rates. Therefore an urgent
need for a tissue engineered alternative exists. Many biomaterials have been developed
during the last decades to fill such defects.
However, these materials do not perform as
well as autologous bone graft. Bone tissue
engineering aims at combining a biomaterial
with osteoconductive properties with viable
osteoprogenitor cells to regenerate bone tissues. A major finding in recent years has
been the identification of osteoprogenitor
cells within bone marrow aspirates. These
cells appeared to have stem cell characteristics, especially when combined with an appropriate 3D scaffold. A potential advantage
of the cell-based technique is the possibility
to engineer almost unlimited quantities of
autologous-like bone tissue. The experimental Surgery group is involved with several
studies in this area.
Group: Experimental Surgery
HLA-incompatible transplantation of
mesenchymal stem cells for the regeneration of bone in a critical size defect
model in the sheep tibia
The aim of the present project is the in vivo
evaluation of preformed constructs derived
from xenogenic mesenchymal stem cells
and mineralized collagen in terms of their
effect on bone healing of an osseous defect in the sheep tibia. MSCs display special
characteristics in their immunological behavior that suggest that HLA-incompatible
cell transplantation may be possible. Since
no relevant models are available for allogenic transplantation of human MSCs, xenogenic and, thus, maximally HLA-incompatible transplantation is planned for the
present project. If the human MSCs become
integrated and contribute to bone healing
in the sheep model, i.e. under conditions
of maximal immunological incompatibility,
then they should work well for inter-human
allogenic transplantation. On this basis and
in contrast to autologous cells that have to
be harvested from each individual patient
and subsequently expanded in culture over
several weeks, human MSCs could be introduced into clinical application as “universal
donor cells”, that offer the advantage of immediate availability. The latter would broaden the scope of indications for all acute interventions and would also be of enormous
economic advantage because the expensive
process of pre-culturing would no longer be
necessary. The data demonstrates that the
model works well for evaluation of stem
cells from different origins for their ability
to regenerate bone in large bone defects. In
comparison to the transplantation of empty
matrices, the transplantation of human xenogenic MSC leads to superior results. However, not as good as those results seen with
autologous mesenchymal stem cells. Future
studies are necessary to evaluate if the elimination of the cells or decreased response of
the human MSC to the local osteoinductive
influence in the sheep bone defect are responsible for this observation.
Partners: P. Niemeyer, Freiburg University,
W. Richter, Heidelberg University, Germany
Critical size defect model in osteoporotic
rats as screening method for new treatment technologies
Healing of large bone defects (3 to 8 cm) is a
significant clinical problem for people of all
ages and health status. While autogenous
grafting is a very good treatment option, significant morbidity and a limited supply of
autogenous bone have resulted in considerable research efforts to establish a tissue engineered approach. However, finding a useful
tissue engineered solution for osteoporotic
patients may be particularly problematic as
the osteogenic and osteoinductive quality
of autogenous tissues may be diminished.
Also the ability of host tissues to respond
to the implanted graft may not be the same
as for healthy individuals. Therefore a standardised model is required for evaluation
of new treatment modalities in large bone
defect healing in osteoporotic patients. We
intended to have a positive control consisting of bone graft harvested from syngeneic
animals and a negative group consisting of
an empty defect. 48 Female Wistar rats were
used in this study. All animals were operated
at 17 weeks of age to create a large bone
defect (5 mm ostectomy) of the femur. The
defect was stabilised using a custom made
radiolucent PEEK plate with angular stable
screws. In half of the rats, osteoporosis was
induced 5 weeks before the defect surgery
via a bilateral ovariectomy (OVX group). All
animals were sacrificed 9 weeks following
defect surgery. Computed tomography was
performed at the time of ovariectomy, and
in all rats at the time of defect creation and
again at sacrifice. Radiographs were performed weekly following defect creation.
The OVX group showed approximately 50%
bone mineral density loss in the femur after 5 weeks. There was no complete bone
healing seen in the negative control group.
A small conical extension of bone could be
detected along the plate until week 4, but no
further progression of bone healing could be
detected after this time. The bone graft group
demonstrated good healing in some animals
at an early time period. To our knowledge,
this is the first description of a model for
evaluating the effect of osteoporosis on bone
healing in a large bone defect model in rats.
The custom made implants provided good
stability for this model, including bone of
poor quality as seen in the ovariectomised
individuals.
Partners: P. Schawalder, Vetsuisse Faculty,
University of Berne, Switzerland. AO Development Institute, Davos, Switzerland
In vivo corrosion of three guide wires
(MP35N, L605 & 316L) in combination
with a conventional 316L stainless steel
cannulated screw
When using conventional guide wires there
is a possibility that the wire breaks off at
the tip of the screw and remains in contact
with the screw, or worse, a part of the wire
is still in the canal of the screw. In both cases
the wire fragment cannot be removed surgically without major trauma to the patient.
A broken instrument becomes an implant
and must fulfill the biological requirements
of implantable material (biotolerance). Since
interest has developed in the use of novel
materials (MP35N or L605) for guidewires,
instead of the conventional 316L, the combination of these materials with 316L and
titanium cannulated screws must be investigated. MP35N is a Nickel-Cobalt-ChromiumMolybdenum based biocompatible alloy that
has unique combinations of properties – ultra
high tensile-strength, toughness, ductility,
high modulus of elasticity (E) and outstanding corrosion resistance as a simple metal.
It can also be cold worked and thermally
aged to very high yield strengths. L605 is
a Cobalt-Nickel-Chromium-Tungsten based
alloy with similar properties. MP35N and
L605 are generally recommended for applications where a combination of high
strength, high modulus values and good corrosion resistance are required. Both alloys
are already widely used as medical implants.
Therefore these properties make these alloys
attractive options as guide wires. The purpose of this study is to exclude the possibility
of experiencing complications due to adopting MP35N or L605 as a guide wires for cannulated instruments of dissimilar material
(ie 316L stainless steel), that are worse than
would be expected from currently used 316L
guide wires. The outcome of in vitro studies
suggests that the potential for corrosion is
hard to predict in an in vivo environment,
and will be affected by the local fluid environment. Despite the comprehensive evaluation of tissue from the animals in this study,
we cannot guarantee that no corrosion was
occurring, but to the best of our abilities, we
could not detect an adverse in vivo effect of
using dissimilar materials (Co-Cr alloy with
stainless steel) compared with stainless steel
alone in a model of a broken guide wire in a
cannulated screw.
Partners: AOTK, Synthes Inc. Paoli PA, USA
able composite, based on poly (L-lactic acid)
(PLA) and ß-tricalcium phosphate (ß-TCP),
was developed by a non solvent technique.
Its in vivo biocompatibility was demonstrated in rodents (Montjovent MO et al. Tissue
Eng. 2005 Nov–Dec;11(11–12):1640-9.), but
it must now be considered in a large animal
model, before going to a human application. As a first step, the composite is tested
as bone void filler. Chronos™ was chosen
as a control as it is a currently marketed
product that allows comparison between a
ceramic based scaffold and a polymer based
scaffold. Data is only available from the short
and mid term timepoints. Although no signs
of inflammation were seen, a fibrous tissue layer isolated the biocomposite scaffold
from the surrounding bone. Minimal bone
ingrowth into the biocomposite was evident
with CT and histomorphometry, which was
also supported by the reduced ultrasound
velocities. These short and medium term results do not support clinical usage in the cancellous region of long bones on the grounds
of poor osteoconductive and biocompatible
parameters compared with currently available products.
Partners: D. Pioletti, L. Matthieu, EPFL,
Lausanne, Switzerland
Bioresorbable composite as bone substitute – In vivo study in sheep
Bone, a natural cellular composite, is one of
the most frequently repaired tissue. Surgeons
currently use either auto- or allo-grafts,
which, however, have a limited availability,
or present pathogen transmission risks, respectively. Synthetic tissue grafts are therefore investigated in order to provide porous
scaffolds, seeded with the appropriate type
of cells, as templates for tissue regeneration.
Polymer or ceramic scaffolds are mainly used
today, although they present inadequate
mechanical properties for bone tissue regeneration. Ceramics are intrinsically brittle
and can break into peaces when implanted.
Polymers have a low modulus compared to
bone modulus, thus tend to collapse when
submitted to external stress in the body. Using a composite we have obtained scaffolds
with a more ductile behaviour than pure
ceramics, and higher resistance than a pure
polymer. Therefore, we are focusing on this
bioresorbable polymer-ceramic composite,
obtained with properties similar to those
of natural cancellous bone. This bioresorb30 | Activity Report 2007
Cartilage repair using a specific articular
progenitor cell
Focal articular defects commonly occur as
a result of trauma to the articular cartilage.
This may be a consequence of a sporting
injury, or other traumatic injuries. Cartilage
defects over a certain critical size fail to heal
and degenerate, resulting in debilitating arthritis. These injuries often occur in young,
otherwise healthy patients, and may result
in a significant decrease in quality of life.
The current ‘Gold Standard’ for the biological repair of localized cartilage defects is Autologous Chondrocyte Implantation (ACI).
While the benefits of this technique are unquestioned, there remain, however, both
clinical and biological, problems. Clinically,
the major drawback is that it requires two
major operative procedures. Biologically, we
are unable to control the type of repair tissue
generated varying between fibrous to hyaline tissue. Furthermore, we do not know
the requirements that will ensure good integration between repair and host tissue, and
there is a limitation to the size of defect that
can be treated which is a function of the
number of cells that can be generated from
cartilage harvested around the periphery
of the joint. Using progenitor cells isolated
from the surface of articular cartilage may
avoid the necessity for obtaining such large
amounts of cartilage as greater amplification is possible in vitro, and may provide a
more reliable, superior cartilage repair matrix compared with the ACI procedure.
Long term time-points in a goat model are
being used, an important consideration in
evaluating new techniques for cartilage
healing. Thus at this point, no data are available, but it is expected that the progenitor
cells will produce a superior cartilage matrix
for repair of defects compared with the ACI
technique in terms of histological parameters, biomechanical properties and integration to the host cartilage. It is believed that
the progenitor cells will have a less variable
morphology and be a superior matrix because the progenitor cell has the developmental ability to recreate articular cartilage
unlike the mixture of chondrocytes types
being used currently in ACI procedures.
Partners: H. McCarthy, C. Archer, University of Cardiff, Great Britain
Titanium VPS coating to increase bone
ongrowth of carbon fibre PEEK implants
Polyetheretherketone (PEEK) is a composite thermoplastic biomaterial exhibiting biochemical and biomechanical properties suitable for load-bearing orthopaedic implants.
Two advantages of carbon fibre reinforced
PEEK (CFR PEEK) is its increased biomechanical properties and superior wear resistance. These properties are required for
long-term orthopaedic implants such as joint
prosthesis and spinal cages. However the
hydrophobic surface of CFR PEEK implants
induces the deposition of a peri-implant fibrous capsule preventing bone apposition
which is unfavourable for stable anchorage
of implants. Nevertheless this tissue reaction
can be avoided by coating PEEK implants
with materials known to encourage bone
tissue ongrowth such as hydroxyapatite or
titanium. The objectives of the present study
was to compare the bone apposition on uncoated CFR PEEK screws to VPS Titanium
coated CFR PEEK screws by investigating
implant torque removal and bone/implant
contact area.
Twenty healthy mature adult female Swiss
Alpine Sheep were included in this study.
They were part of a larger study investigating bone healing using a tibia critical size
defect model. In this model, a 7-hole custom
made CFR PEEK plate and a 7 hole LCP
were applied on the medial and cranial aspect of the tibia respectively. The CFR PEEK
plate was locked with randomly chosen uncoated or VPS titanium coated CFR PEEK
screws. Screw treatment was alternated between the two proximal and two distal holes
of the CFR PEEK plate (the middle three
holes remained empty). The sheep were
euthanized 6 months postoperatively. The
proximal screws were left in situ for histomorphometric analysis and torque removal
measurements were performed on remaining screws.
The mean torque removal of the titanium
VPS coated screws was significantly greater
than that of uncoated screws (4.97 ± 1.54 Nm
versus 2.3 ± 0.81 Nm; P< 0.001). None of
the uncoated screws failed during torque removal and all the coated screws failed during torque removal. the VPS titanium coated
CF PEEK screws had a significantly higher
percentage of bone/screw interface than uncoated CF PEEK screws (50% versus 1%;
P<0.001) markedly more bone on growth
compared to non coated CF PEEK screws.
Partners: P. Schawalder, Vetsuisse Faculty,
University of Berne, Switzerland; H. Gruner, Medicoat AG, Mägenwil, Switzerland;
R. Wieling, Icotec, Altstätten, Switzerland
Groups: Experimental Surgery, Tissue
Morphology
Development of a model for testing biomaterials used for implant anchorage in
poor quality bone
Poor quality bone stock at the location of
implants being used for osteosynthesis can
occur as a result of improper surgical technique (screw stripping), traumatic injuries
(comminution) and due to metabolic disease
such as osteoporosis. In these cases biomaterials are being developed to provide secure
anchorage of implants at these sites. A large
animal model is required for testing these
biomaterials intended for this use in human
patients. We have developed a distal femoral
osteotomy model secured by a custom-made
LCP, designed to fit the topography of the
distal femur in Swiss alpine sheep. The osteotomy was made at the level just proximal to the attachment of the gastrocnemius
caudally and the femoropatellar joint pouch
cranially. The custom made plate has three
holes for locking screws in the plate distal
to the level of the osteotomy, and four holes
proximal to the level of the osteotomy. An
additional device has been made to be placed
into the drill holes distal to the osteotomy
(metaphysis/epiphysis) such that a cutting
tooth can be activated, and the cancellous
bone removed to create a cavity larger than
the screw but the thin outer cortical rim is
left intact. Mechanical testing in cadaveric
tissue demonstrates that the unfilled cavity
provides poor resistance to torsion compared
with the construct when the cancellous bone
is left intact.
The in vivo model has been validated in
which the healing of the osteotomy is compared and used to evaluate the efficacy of
biomaterials for providing anchorage of
these distal screws in the custom-made plate
and therefore rigidity of the construct.
Partner: Synthes Inc., Paoli PA, USA
Groups: Experimental Surgery, Research
Services
A novel sheep model for evaluating biomaterials in cancellous bone
The use of sheep cancellous bone models has
been described to assess new orthopaedic
biomaterials. However, sheep have a limited
availability of cancellous bone for implantation of materials making it difficult to find
multiple comparable sites within an individual animal. The purpose of this study was
to develop a novel sheep model in which
multiple samples could be evaluated in cancellous bone within the same animal. This
model uses only the distal femur and proximal tibia to optimise standardisation of the
local environment of the tested implants. Cadaver studies were performed to determine
both the extent of cancellous bone location
in the ovine distal femur and proximal tibia
and to design and develop appropriate drilling jigs. Mature, female, Swiss Alpine sheep
were obtained from a flock maintained for
orthopaedic research, such that size, shape
and age were standardized, and the health
status known. Cylinders (5mm x 15mm) of
bioresorbable polymer-ceramic composite,
based on poly (L-lactic acid) (PLA) and ß-tricalcium phosphate (ß-TCP) were implanted
in the distal femur and proximal tibia during
a bioperformance in vivo study and 316L
stainless steel cannulated screws in combination with guide wires of different material
were implanted during an in vivo corrosion
study. Thirty sheep were included in various studies. No postoperative complications
were recorded in 28 sheep. Two sheep were
euthanized within 2 weeks of surgery: one
with unresponsive pleuropneumonia and
one with septic femoro-tibial arthritis. The
described techniques allowed the insertion
of 10 implants per animal. The designed jigs
allowed accurate and reliable placement of
all the implants in cancellous bone. This abstract describes a useful, low-morbidity, animal model for testing multiple biomaterials
in cancellous bone in the same animal. Differences exist in the trabecular structure of
the proximal tibia compared with the distal
femur which should be considered in the experimental design. The size of implants tested
is also limited. However the condensed spatial assignment of samples ensures shorter
surgery times, the opportunity for effective
local anaesthesia, and more similar loading
patterns and amounts of overlying soft tissue
compared with other models. The technique
also allows accurate harvest of implants, performed by coring out a bone plug surrounding the implant for detailed imaging and histological analysis.
Ankle joint pressure in pes cavovarus
Cavovarus is a complex deformity thought to
occur from muscular imbalance of idiopathic
or neurological origin. The pathology of the
deformity consists of a plantarflexed medial
forefoot which accentuates or contributes to
hindfoot varus and dorsiflexion of the talus.
Consequently, the biomechanics of the ankle
are affected and may lead to lateral hindfoot
instability. It is suggested that longstanding
ankle incongruence of the cavovarus deformity alone increases the contact stresses in
the ankle joint enough to lead to anteromedial ankle arthrosis. The purpose of this
study was to investigate the biomechanical
characteristics of the ankle joint in cavovarus deformity. We postulated that cavovarus
causes changes of the pressure distribution
in the ankle. Ten fresh-frozen cadaver lower
legs without deformities, prior trauma or
arthrosis were used. The skin and subcutaneous tissue were removed, and ligaments
and capsules preserved. A cavovarus foot deformity was simulated by inserting metallic
wedges of 15° and 30° dorsally into the first
tarsometatarsal joint. Pressure sensors were
placed in the ankle joint to record tibiotalar pressure distribution. Axial compression
via the tibia and fibula was increased continuously from 50 N preload to 700 N (corresponding to mean body-weight). Maximum
load was held for six seconds prior to complete unloading. Load, crosshead displacement and contact pressure distribution of
the sensor were captured at 50 Hz. The peak
pressure increased significantly from neutral
alignment to the 30° cavus deformity, and
the centre of force migrated medially. The
anterior migration of the centre of force was
significant for both the 15° (p = 0.021) and
the 30° (p = 0.007) cavus deformity. Differences in ligament laxity did not influence
the peak pressure. These findings support
the hypothesis that the cavovarus foot deformity causes an increase in anteromedial
ankle joint pressure leading to anteromedial
arthrosis in the long term, even in the absence of lateral hindfoot instability.
Partners: M. Weber, F. Krause, Department
of Orthopaedic Surgery, Inselspital, Berne,
Switzerland
Group: Research Services
Does screw angulation increase pullout
strength of locked screw-plate constructs
in cancellous bone?
Clinical results of plates with locked angled
screws (e.g. PHILOS) are promising. It has
been shown experimentally in a foam model that locked screw angulation decreases
pullout strength. The discrepancy may be
due to foam not adequately simulating bone
properties with respect to pullout failure
of such constructs. This study investigated
the effect of screw angulation upon pullout strength of locked screw-plate constructs
in cancellous bone specimens. Cancellous
bone blocks were machined from bovine
femoral condyles and bone mineral density
(BMD) determined. 3 groups (n=8) were instrumented with custom made plates with
2 locked screws (5mm diameter) at 3 different screw angulations: 0° (straight), 10°
and 20° diverging. Screws were completely
inserted through the material. Pullout tests
were performed and pullout strength determined. Correlation analysis and analysis
of covariance with BMD as covariate were
performed. High correlations between BMD
and pullout strength were obtained for every group (R2>0.876). Pullout strength was
significantly lower at 20° compared to both
0° and 10° screw angulation (p<0.001). The
findings in foam were reconfirmed in cancellous bone. Screw angulation of 20° does not
increase pullout strength of locked screwplate constructs but even reduces it. The
foam material cannot be the explanation for
the reduced pullout force. One reason may
be that diverging locked screws induce not
only shear but also compressive stresses at
the upper half of the screw thread cylinder.
At the same time, load transfer at the lower
part is compromised, which both may lead
to premature failure.
Partners: S. Perren, AO Research Institute,
Davos
Mechanical comparison in cadaver specimens of three different 90-degree double-plate osteosyntheses for simulated
C2-type distal humerus fractures with
varying bone densities
Goal of the study was to investigate the boneimplant-anchorage of 90-degree doubleplate osteosynthesis in simulated complete
intra-articular distal humerus fractures using
conventional reconstruction plates (CRP),
locking compression plates (LCP), and distal humerus plates (DHP), depending on the
bone mineral density (BMD) of the cadaver
specimens. Groups (CRP, LCP, DHP, n = 8;
LCP, DHP, n = 13) in distal humerus cadaver
bones were created based on BMD. The fracture model was an unstable intraarticular
distal humerus fracture with a transverse
osteotomy gap representing metaphyseal
comminution (AO type 13-C2.3). Flexion
and extension stiffness as well as cycles until failure due to screw pullout under cyclic
loading were evaluated. Estimates of BMD
values, below which failure was likely to occur, were determined. Stiffness values were
not significantly different between groups
(extension: P = 0.881, flexion: P = 0.547).
Under cyclic loading, consistent screw pull-
out failure occurred at BMD values below
about 400 mg/cm3 for CRP and below about
300 mg/cm3 for LCP constructs. Comparing
BMD-matched groups of 8 and 13 specimens
respectively, the failure rate was significantly
lower for the DHP (0/8) than for the CRP
(5/8; P = 0.026) and tended to be lower
for the DHP (0/13) as compared to the LCP
(4/13; P = 0.096). Bone-implant anchorage
was different between locking and nonlocking plate constructs and depended on BMD.
While in good bone quality implant choice
was not critical, both locking plates provided
superior resistance against screw loosening
as compared to the CRP at low BMD values
(<420 mg/cm3). Based on our laboratory results, we conclude that locking plates such
as the LCP and DHP are constructs designed
to keep anatomical reduction in the presence of comminution and poor bone quality
in a low intraarticular fracture of the distal
humerus.
Partners: I. Schuster, Department of Orthopaedics and Trauma Surgery, University of
Freiburg, Germany; J. Korner, Department
of Trauma Surgery, University of Mainz,
Germany; D. Andermatt, Synthes Inc., Paoli
PA, USA
Adjacent vertebral failure after vertebroplasty: a biomechanical study of lowmodulus PMMA cement
PMMA is the most common bone substitute
used for vertebroplasty. An increased fracture rate of the adjacent vertebrae has been
observed after vertebroplasty. Decreased failure strength has been noted in a laboratory
study of augmented functional spine units
(FSUs), where the adjacent, non-augmented
vertebral body always failed. This may provide evidence that rigid cement augmentation may facilitate the subsequent collapse of
the adjacent vertebrae. The purpose of this
study was to evaluate whether the decrease
in failure strength of augmented FSUs can
be avoided using low-modulus PMMA bone
cement. In cadaveric FSUs, overall stiffness,
failure strength and stiffness of the two vertebral bodies were determined under compression for both the treated and untreated
specimens. Augmentation was performed
on the caudal vertebrae with either regular or low-modulus PMMA. Endplate and
wedge-shaped fractures occurred in the cra34 | Activity Report 2007
nial and caudal vertebrae in the ratios endplate:wedge (cranial:caudal): 3:8 (5:6), 4:7
(7:4) and 10:1 (10:1) for control, low-modulus and regular cement group, respectively.
The mean failure strength was 3.3 +/- 1 MPa
with low-modulus cement, 2.9 +/- 1.2 MPa
with regular cement and 3.6 +/- 1.3 MPa for
the control group. Differences between the
groups were not significant (p = 0.754 and
p = 0.375, respectively, for low-modulus cement vs. control and regular cement vs. control). Overall FSU stiffness was not significantly affected by augmentation. Significant
differences were observed for the stiffness
differences of the cranial to the caudal vertebral body for the regular PMMA group to
the other groups (p< 0.003). The individual
vertebral stiffness values clearly showed the
stiffening effect of the regular cement and
the lesser alteration of the stiffness of the
augmented vertebrae using the low-modulus PMMA compared to the control group
(p=0.999). In vitro biomechanical study and
biomechanical evaluation of the hypothesis
state that the failure strength of augmented
functional spine units could be better preserved using low-modulus PMMA in comparison to regular PMMA cement.
Partner: P. Heini, Orthopedic Surgery, Inselspital, University of Berne, Switzerland
Mechanical torque measurement predicts
load to implant cut-out: a biomechanical study investigating DHS anchorage in
femoral heads
Bone strength plays an important role in
implant anchorage. Bone mineral density
(BMD) is used as surrogate parameter to
quantify bone strength and to predict implant anchorage. BMD can be measured by
means of quantitative computer tomography (QCT) or dual energy X-ray absorptiometry (DXA). These noninvasive methods
for BMD measurement are not available
pre- or intra-operatively. Instead, the surgeon could determine bone strength by
direct mechanical measurement. We have
evaluated mechanical torque measurement
for (A) its capability to quantify local bone
strength and (B) its predictive value towards
load at implant cut-out. Our experimental
study was performed using sixteen paired
human cadaver proximal femurs. BMD was
determined for all specimens by QCT. The
torque to breakaway of the cancellous bone
structure (peak torque) was measured by
means of a mechanical probe at the exact
position of subsequent DHS placement. The
fixation strength of the DHS achieved was
assessed by cyclic loading in a stepwise protocol beginning with 1,500 N increasing 500
N every 5,000 cycles until 4,000 N. A highly
significant correlation of peak torque with
BMD (QCT) was found (r= 0.902, P< 0.001).
Peak torque correlated highly significant
with the load at implant cut-out (r= 0.795,
P< 0.001). All specimens with a measured
peak torque below 6.79 Nm failed at the first
load level of 1,500 N. The specimens with a
peak torque above 8.63 Nm survived until
the last load level of 4,000 N. Mechanical
peak torque measurement is able to quantify bone strength. In an experimental setup,
peak torque identifies those specimens that
are likely to fail at low load. In clinical routine, implant migration and cut-out depend
on several parameters, which are difficult to
control, such as fracture type, fracture reduction achieved, and implant position. The
predictive value of peak torque towards cutout in a clinical set-up therefore has to be
carefully validated.
Partner: N. Suhm, T. Kaup, M. Hänni, AO
Development Institute, Davos, Switzerland
Solid body augmentation for comminuted
calcaneal fractures: Development and
biomechanical testing of a hybrid osteosynthesis technique
Comminuted calcaneal fractures are a consequence of high impact trauma to the foot.
Stable fixation and anatomically correct repositioning of the joint surfaces are often
a problem. To improve fracture treatment,
surgical techniques in combination with
new augmentation materials have been
tested. This study presents a new concept
of osteosynthesis of complex calcaneal fractures in combination with an alternative
augmentation technique. Solid body augmentation was developed and mechanically
tested against standard techniques. The solid
body was used for augmentation of a central
fracture void in combination with conventional plating. The results show a statistically
significant higher stability of the new hybrid
osteosynthesis concept against conventional
plating techniques under in-vitro conditions.
This work investigated a new concept of internal support of multifragmentary calcaneal
fractures. Augmentation of defect voids in
the calcaneus with a mechanically stable solid body implant in combination with stable
screw anchorage in this implant leads to a
higher stability compared to plate-fixation
and augmentation with cancellous bone under in-vitro conditions.
Partners: S. Brodt, A. Gisep, AO Development Institute, Davos, Switzerland
Accuracy of fragment positioning following the TPLO procedure and the effect on
biomechanical stability
Tibia Plateau Leveling Osteotomy (TPLO) is
a surgical procedure developed for treatment
of cranial cruciate ligament deficient stifles
in dogs. TPLO is proposed to functionally
stabilize the stifle joint during weight bearing, by decreasing the cranial tibial thrust in
cruciate deficient dogs. The purpose of the
study was to compare the tibial plateau rotation after TPLO procedure to the radiographically planned rotation and to determine the
effect of translations and rotations of the
tibial plateau fragment on the biomechanical
stability of the construct under cyclic loading. 18 cadaveric canine hind limbs were
used. Titanium pins were inserted into the
tibial plateau and the proximal metaphysis
to track the fragment movements by means
of computed tomography-imaging (CT-imaging). CT-scans were performed at three
stages: 1) prior to osteotomy (intact bone),
2) following osteotomy and tibial plateau
rotation (temporarily affixed) and 3) after
completion of the TPLO procedure and stabilization with plate and screws. The bones
were then cyclically loaded in axial compression. The radiographically planned tibial
plateau rotation correlated significantly with
the achieved rotation (r= 0.72, p= 0.001),
although deviations of up to 5.4° were observed. A significant correlation between the
amount of rotation about the sawing axis of
the tibial plateau fragment (CT-scan 1 to 3)
and the plastic deformation of the construct
after 30,000 test-cycles could be found (r=
0.54, p= 0.026). Furthermore, the plastic deformation correlated significantly with the
displacement amplitude at the beginning of
the test (measure for fracture reduction; (r=
0.52, p= 0.035). This study shows that lower
degree of rotation about the sawing axis and
careful fracture reduction are beneficial for
biomechanical stability.
Partner: K. Johnson, College of Veterinary
Medicine, Ohio State University, Columbus
OH, USA
Groups: Research Services, Experimental
Surgery
Factors affecting the stability of screws
in human cortical osteoporotic bone: a
cadaver study
We investigated several factors which affect
the stability of cortical screws in osteoporotic
bone using 18 femora from cadavers of women aged between 45 and 96 years (mean 76).
We performed bone densitometry to measure the bone mineral density of the cortical
and cancellous bone of the shaft and head of
the femur, respectively. The thickness and
overall bone mass of the cortical layer of the
shaft of the femur were measured using a
microCT scanner. The force required to pullout a 3.5 mm titanium cortical bone screw
was determined after standardised insertion
into specimens of the cortex of the femoral
shaft. A significant correlation was found between the pull-out strength and the overall
bone mass of the cortical layer (r2= 0.867,
p< 0.01) and also between its thickness
(r2 = 0.826, p< 0.01) and bone mineral
density (r2= 0.861, p< 0.01). There was no
statistically significant correlation between
the age of the donor and the pull-out force
(p= 0.246), the cortical thickness (p= 0.199),
the bone mineral density (p= 0.697) or the
level of osteoporosis (p= 0.378). We conclude that the overall bone mass, the thickness and the bone mineral density of the
cortical layer, are the main factors which affect the stability of a screw in human female
osteoporotic cortical bone.
Partners: C. Lill, Orthopedic Clinic, Munich,
Germany
Biomechanical testing of different osteosynthesis systems for segmental resection of the mandible
This investigation assessed the mechanical
behavior of 3 different locking and nonlocking reconstruction systems-Unilock 2.4,
Reconstruction 2.4, and Reconstruction 2.7with regard to plate and screw fracture. Five
different plate/screw configurations (Unilock
2.4-locking screws, Unilock 2.4 -conventional screws, Reconstruction 2.4-conventional
screws, Reconstruction 2.7-conventional
screws, and Unilock 2.4-locking screws with
a 1-mm gap; Synthes, Umkirch, Germany)
were tested on synthetic mandibles. All mandibles were resected on the left side between
the canine and third molar, reconstructed,
and loaded cyclically between 30 and 300N
up to 250,000 cycles or until screw or plate
failure occurred. No screw fractures were
observed. All plates fractured close to the
distal fragment. The Unilock plates fixed
with locking screws withstood significantly
more cycles until failure than the Reconstruction plates 2.4 fixed with conventional
MF-Cortex screws. No significant differences
were found in the other groups. Only 2 of
the 34 plates tested, both of the Reconstruction 2.7 system, reached the runout limit.
Unilock plates fixed with locking screws
have a higher long-term stability than the
Reconstruction 2.4 system. A 1-mm gap between the plate and mandible does not lead
to early screw failure in the Unilock 2.4 system with locking screws. The Reconstruction
2.7 system seems superior if well contoured,
because 2 of those plates reached the runout
limit; however, this system is not as easy to
handle as the 2.4 systems, and good contouring is difficult to achieve. Therefore, we
consider the Unilock 2.4 system with locking
screws the best choice.
Partners: W. Schupp, Department of Oral
and Maxillofacial Surgery, University Hospital Freiburg, Germany
Biomechanical evaluation of a new technique using staples for patella fracture
fixation
Transverse patella fractures are common fractures. Because the patella plays an important
role in knee function, effective treatment of
patella fractures is essential. Fractures with
articular incongruity of more than 2–3mm
are believed to be at increased risk to develop post-traumatic osteoarthritis because of
the high contact forces in the patellofemoral
joint. Although other methods have been
proposed (as screw fixation) tension band
wiring is the gold standard for fixation of
transverse patella fractures. However, it can
be difficult to secure the tension band wire
directly down against the patella, allowing
the fragments to slip apart with quadriceps
contraction. A new technique is based on
memory metal staples inserted across the
fracture. The advantages of the new technique could be reduced surgical time because of the ease of staple application and
less risk of skin irritation. However, no tests
have been conducted so far to prove adequate biomechanical stability as compared to
tension band wiring. Eight human cadaveric
knees with intact joint capsule, quadriceps
and patella tendons were used. After generation of a transverse patella fracture, each
specimen was consecutively instrumented
in a randomised manner with tension band
wiring and the new staple technique applying two nickel-titanium staples. The lower
leg was simulated with a weight attached
to the tibia. The specimens were fixed via
the femur to the table of a material testing
machine. A cyclic load ranging from 20N
to 300N was introduced via the quadriceps
tendon to generate flexion/extension of
the knee joint for 5000 cycles. The motion
at the anterior (stretch side) and posterior
(joint side) site of the transverse fracture
was determined with a video optic measurement system. An opening of the fracture gap
of 2mm was defined as failure. A survival
analysis was performed based on the cycles
until failure. The survival probability was
significantly higher for the staple group as
compared to the tension band wiring group
(p= 0.044). Additionally, the motion at the
fracture site was significantly lower for the
staple group (joint side: p= 0.031; stretch
side: p= 0.003). Based on the results of this
study, the staple technique is a promising
alternative to tension band wiring of transverse patella fractures.
Partners: A. Appelt, University Hospital
Heidelberg, Germany
Biomechanical investigation of the stability and failure mode of an intramedul-
lary nail with and without angular stable
locking bolts for treatment of distal tibia
fractures
A stable fixation of tibial fractures with intramedullary nails becomes more difficult
the further the fracture is located distally.
Angular stable locking bolts may increase
osteosynthesis stability. Purpose of this study
was to investigate the osteosynthesis stability of a nail with and without angular stable
locking bolts under cyclic loading conditions.
Additionally, as the load transfer mechanism
between bone and nail is different for the
two systems, it should be investigated if the
failure mode is different for angular stable
and conventional nails. Left and right bones
of eight pairs of human cadaveric tibiae were
randomly assigned to either of two treatment groups: 1) Expert Tibia Nail (ETN, Synthes Inc.) with and 2) ETN without angular
stable locking bolts. Bone mineral density
(BMD) was determined at the distal tibia. A
transverse osteotomy (7mm gap) was created 10mm on the proximal side of the distal
screws to simulate an unstable 43-A1.3 fracture after unreamed instrumentation with
9mm nails. Specimens were loaded in eccentric, axial compression with superimposed
internal rotation for a maximum of 250,000
cycles. Rotational and translational movements were recorded at the osteotomy site
using a 3D motion analysis system. Failure
mode and cycles until failure were recorded.
Only the bone pair with the highest BMD
(0.47g/cm3) survived. The other specimens
failed predominantly by breakage of the
most proximal of the distal bolts in both
groups (angular stable: n= 6, conventional: n= 4). Cycles until failure were not significantly different between the two groups
(p= 0.426) with a trend for higher cycle
numbers for bones with higher BMD. Lower
rotational and translational movements were
observed for specimens with BMD < 0.3 g/
cm3 and increased nail-isthmus distance at
the fracture site. This study demonstrated
that angular stable locking of the bolts improved osteosynthesis stability compared to
the non locked version in a distal tibia fracture model – especially in poor bone quality.
Based on the results obtained, an increased
rate of bolt breakages when using angular
stable bolts is not expected clinically.
Partners: D. Höntzsch, D. Albrecht, BG
Trauma Clinic Tübingen, Tübingen, Germany
Decreasing strains at the implant-bone
interface: A new design to reduce the risk
of pin loosening.
The use of external fixators (EF) is limited
by the strain at the implant-bone interface.
Bending of conventional pins may result
in critical bone strains (higher than about
5000μstrain) at the inner and outer cortex
of a long bone depending on material properties and geometry of the EF components.
This leads to bone resorption and pin loosening. A new load transfer concept was developed which relies on a novel pin-sleeve (PS)
system to decrease bone strains at the interface with the EF pins. The goal of this experimental study was to model and compare the
strain at the implant bone interface generated by the new system and the one generated
by a commercially available transfixation pin
(TP). Two canevasit hollow cylinders (CHC)
as diaphyseal bone models were instrumented with either the conventional TP or
the new PS system. The latter consisted of a
5-mm diameter pin running through an
8-mm diameter sleeve inserted into the
CHC. Pin and sleeve were in contact at two
1mm wide inner sleeve supports located at
the centre of each cortex. The 6.3-mm diameter, positive and centrally threaded TP was
applied in a standard manner. Strain gages
(SGs) were glued on the external surface
of the CHCs centred 4.5mm above the implants. The outer support for both systems
was a resin fiber 10 mm thick cast. In four
different tests with the new PS system preloading of 3, 4.5, 5.5 and 6kN was applied
to the threaded pin using nuts via a ring
incorporated into the cast. The lower end of
the cast was embedded in PMMA and fixed
to the table of a material testing machine.
The CHC was loaded in axial compression
(range: 50N–2500N) at 1 Hz for 2000 cycles.
Each configuration was tested three times.
Axial cylinder displacement and strains were
recorded and compared. Finite element models (FEM) of both instrumentation methods
were developed to compute bone strains
near the implants. Validation of the FEM
was performed by comparing strains and displacements between the experimental and
the computational model. Correlation coefficients were computed between preloading
and axial displacement and strains. For every tested preload the PS system had comparable axial displacement with a substantial
decrease in strains as compared to the TP.
Preloading was found to be inversely corre38 | Activity Report 2007
lated to the axial displacement (rP= -0.93; p <
0.01) but did not correlate significantly with
the measured strain (rP= -0.33; p= 0.29).
The FEMs were validated having maximum
error of 14% between the experimental and
FEM strain and displacement values. Based
on these models the maximum strains 2mm
above the implants were 5500μstrain in the
TP and 500μstrain in the PS system. This
study demonstrated that the novel system
has the potential to reduce the risk of pin
loosening and improve the clinical performance of external fixators.
Publications: Patent
Group: Research Services, Experimental
Surgery
Biomechanical investigation of locked
screw-plate systems for fixation of periprosthetic femoral shaft fractures at the
tip of a cemented hip prosthesis
Periprosthetic fractures are potentially problematic and occur most commonly in osteopenic elderly women. The number of
fractures will increase strongly as the life
span of patients and the number of primary
and revision hip arthroplasties continue to
rise. The most common periprosthetic femoral fracture, which is also the most complex
to manage, occurs in the region surrounding
and immediately distal to the stem tip (type
B fracture, Vancouver classification). When
the femoral component remains well-fixed
(type B1 fracture), open reduction and internal fixation is recommended. Many surgeons
prefer the use of plates only for periprosthetic fracture fixation. The clinical problem
of using plates with monocortical proximal
screws is that proximal screw pullout has
been observed. In a recent study the use of
a locking compression plate (LCP) was proposed. The LISS system has also been used in
some cases for periprosthetic fractures of the
femur. Compared to these systems, plates
with angular stable screws which are angulated and thus allow bicortical anchorage in
the prosthesis area may increase fixation stability. The goal of this project is to investigate
the benefit of screw angulation when LCP
plates are used for fracture treatment. 13
pairs of osteopenic, cadaveric human femura
were used. Bone mineral density was determined in the shaft area. All femura were instrumented with Charnley prostheses using
bone cement. To determine the best screw
angulation when using broad LCPs, all specimens were scanned with an ExtremeCT. Due
to the limited bone volume, a screw angulation is not feasible anterior of the femoral
stem. On the posterior side an angulation of
30° was determined to be the best solution.
45° oblique osteotomies were performed at
the prosthesis tip. After complete reduction
of the osteotomy gap the paired femurs were
instrumented with either broad 12 hole LCPs
or modified broad 12 hole LCPs with angulated locked screws on the proximal, posterior side. The distal femur was embedded
with PMMA and mounted in a physiologic
orientation on the servo-hydraulic material
testing machine. Mechanical testing will be
performed in the next project step. Force
transfer to the prosthesis head will be realised by the actuator of the material testing machine. Cyclic loading will be applied
with increasing load amplitude until failure
of the construct. The relative motion at the
osteotomy, determined with a 3D motion
analysis system, will be used to compare the
two experimental groups. We expect less
motion for the plates with the angulated
locked screws.
Partners: P. de Boer, AO Education, CPP
‘Fracture fixation in osteoporotic bone’.
6. Team Members
Director:
Schneider Erich
Prof, Dr sc techn
Vice-Director:
Ito Keita
Prof, MD, ScD
AO Senior Scientific Advisor:
Perren Stephan M.
Rahn Berton
Permanent Scientific Staff:
Alini Mauro
Bouré Loudovic
Gantenbein Benjamin
Grad Sibylle
Eglin David
Milz Stefan
Pearce Simon
Richards R. Geoff
Schlegel Urs
Schwieger Karsten
Stoddart Martin
Verrier Sophie
01.04.97
01.11.94–31.08.07
Prof, Dr med, Dr sci (hc), Chirurg FMH Prof, Dr med, Dr med dent
01.01.64
01.07.68
Prof, PhD
Med vet, MSc, DES, Diplomate ACVS
Dr lic phil nat
Dr sc nat
PhD
PD Dr med
BVSc, PhD, Diplomate ACVS
Prof, PhD, MSc
Dipl med Ing, PhD
Dr Ing
PhD, Mphil, BSc
Dr es Sciences
01.07.99
18.09.06
01.08.04
03.08.00
01.06.06
01.08.04
01.04.05
01.10.91
17.10.88
01.09.03
01.07.05
01.08.04
Temporary Scientific Staff:
Arens Daniel
Dr med vet
01.06.03–30.09.06
01.11.07
Baucke Michelle
Med vet
01.04.07
Braunstein Volker
Dr med
01.08.06
Brianza Stefano
Dr med vet, PhD, Biomed Eng
01.02.07
Brighenti Vittoria
Biomed Eng
01.03.07
Chan Samantha
PhD Cand20.04.06–31.03.07
Chen Yuting
IAESTE Stud
01.08.06–31.08.07
Debefve Laurence
Med vet
03.01.07
Declan Devine
PhD
01.06.07
Denom Jessica
MSc
05.02.07–31.12.07
Duda Sven
Med Stud
09.07.07–30.09.07
Forkmann Christoph
PhD Cand, Dipl Ing
01.01.05
Greulich Franziska
IAESTE Stud
01.10.07
Griffon Stéphane
MSc
05.02.07–31.12.07
Gröngröft Ina
Med vet
01.04.05–31.08.07
Hahn Joachim
Med vet
08.05.06–31.10.07
Hayes Jessica
BSc
12.01.04
Hofmann Adrian Dipl Ing FH
01.12.05–31.01.07
Hoppe Sven
Med
08.01.07
Isaksson Hanna
PhD Cand, MSc
01.10.03–31.12.07
Jähn Katharina
PhD Cand, Dipl Bc
01.04.06
Jünger Svenja
PhD Cand, MSc
09.01.06
Kluge Katharina
Med vet23.05.05–31.10.07
Kupcsik Laszlo
PhD Cand, MSc
01.11.03
Langeraar Judith
Med Stud
16.04.07–14.08.07
Leitner Michael
Med vet
14.11.05–30.11.07
Li Zhen
PhD Cand, BEng
01.11.04–09.05.05
12.05.06–30.04.07
01.05.07
Lippross Sebastian
Dr med
01.02.06–31.03.07
Moriarty Fintan
PhD
19.03.07
Morys Anna
Trainee
04.06.07–10.08.07
Noailly Jérôme
MD
15.01.07
Pearce Alexandra
Dr med vet
01.05.05–31.10.07
Poser Livia
PhD Cand, Med vet
15.08.05–31.10.07
Potier Esther
PhD
13.11.06
Poulsson Alexandrea
PhD29.08.06
Pucher Melanie
Med vet
01.11.05–31.10.07
Randau Thomas
Med
01.04.06–31.03.06
Rindermann Georg
Med vet
01.11.06
Seidenglanz Ulrike
Med vet
01.06.06
Tami Andrea
Dr sc techn ETH
07.11.05
Terhorst Sandra
Dr med
01.07.03–17.10.04
01.08.05–09.10.05
27.02.06–16.04.06
01.08.06–15.10.06
24.04.07–25.05.07
van der Werf Marije
PhD Cand, MSc
01.08.04
Viehöfer Arnd
Med Cand
12.02.07
Wissing Sandra
Med vet27.08.07
Witte Tanja
Med vet
01.03.07
Zeiter Stephan
Dr med vet
01.06.03
Technical and Service Staff:
Accola Romeo
Agnello Marco
Bentz Ulrich
Bluvol Mauro
Dicht Benno
Erb Peter
Faoro Pierina
Furlong-Jäggi Pamela
Furter Andrea
Geret Vreni
Glarner Markus
Goudsouzian Nora
Gueorguiev Boyko
Haller Manuela
Kaltenbrunner Tina
Kellerhals Patricia
Lanker Urban
Leumann Marianne
Lezuo Patrick
Moor Robert
Müller Gregor
Müller Reto
Oswald Andrea D.
Perren Dominic
Peter Robert
Radtke Roman
Rüegg-Moser Catherine
Senn David
Sprecher Christoph
Steiner-Müller Sandra
Van der Pol Bas
Wahl Dieter
Wahl Sonia
Informatiker
01.04.06–31.12.07
Apprentice
01.08.03–31.07.07
Dipl Ing HTL Mikrotechnik
01.08.07
Laborant (Eidg Fähigkeitsausweis)
01.06.03
Mechaniker (Eidg Fähigkeitsausweis)
01.01.78
Tierpfleger (Eidg Fähigkeitsausweis)
03.05.93
Arztgehilfin (MPA)
01.12.07
Chemikerin FH
01.02.04
Tierpfleger24.04.06
Laborantin (Eidg Fähigkeitsausweis, 20%)
19.08.63
Chem Messtechniker (Eidg Fähigkeitsausweis)
01.11.97
BSc
01.02.02
Dipl Phys
01.03.03
Administrative assistant
01.02.07
Dipl VSA, MRTA Dipl. (80%)
01.04.03–31.07.07
Dr med, MBA (80%)26.06.06–31.03.07
Tierpfleger (Eidg Fähigkeitsausweis, 80%)
16.06.86
Laborantin (Eidg Fähigkeitsausweis, 90%)
02.10.00
Dipl Ing
01.08.03
Laborant (Eidg Fähigkeitausweis, 50%)
17.10.66–31.12.07
Lic phil, Librarian (50%)
17.01.05
Tierpfleger (Eidg Fähigkeitsausweis, 80%)
13.11.01
Apprentice
06.08.07
Tierpfleger
01.02.83
Dipl Laborant HFP
15.09.84
Med Eng Stud
01.11.04–4.04.07
Arztgehilfin (MPA)
01.11.07–21.12.07
Apprentice technician
08.08.05
Dipl Ing FH
01.02.00
Dr Phil II (60%)
02.01.06
Dipl Ing FH
01.09.04
Dipl techn Werkzeugspezialist HFP
01.11.93
Dipl DH Ökonomin HFP
01.12.95
Wenzinger Elsbeth
Wieling Muriel
Wilhelm John
Windolf Markus
Wipf Margrit
Librarian (50%)
Dipl Schneiderin
PhD, Quality Management
Dipl Ing TU
Administrative assistant
Guests:
Coelho Paul Jorge
Habermacher Judith
Madeira Luis Tamissa
Nürnberger Benedikt
o’Halloran Damien
Pokorny Saskia
Scharf Martin
Schnabel Bernd
Schneider Rahel
Schuler Martin
Simpson Angharad
Stepanek Patrick
Van Guyse Maarten
Wenger Barbara
Project MANDREGEN, University of Lisbon, Portugal
Vet Student of VetSuisse Faculty of Veterinary Medicine, University of Bern,
Elective Course
Project MANDREGEN, University of Lisbon, Portugal
Medical Doctor, University of Munich, Germany
PhD Student, collaboration with The National University of Irland, Galway
Bachelor Thesis, Technical Univ Hamburg Harburg, Germany
Project PATSTAPLE, Medical Student, University Hospital Heidelberg
Project PATSTAPLE, Medical Student, University Hospital Heidelberg
Administrative support, University of Bern
Laboratory for Surface Science and Technology, ETH Zurich
Project EXBONE1, Medical Student, Birmingham, GB
Project INTERFRAC4, Dr Ing, Technical University Hamburg-Harburg
Project EXBONE1, Scientific Dr at Katholieke Univ Leuven, Belgium
Vet Student of VetSuisse Faculty of Veterinary Medicine, University of Bern,
Elective Course
15.03.93–31.12.07
01.01.96
01.02.01–31.07.07
01.11.04
01.12.01
1
2
3
4
7. Publications
Original Articles
1. Arens D, Sigrist I, Alini M, Schneider E, Egermann M: Seasonal changes of bone metabolism in
sheep. Vet J 174:585–591, 2007
2. Auer JA, Goodship A, Arnoczky S, Pearce S, Price J, Claes L, von Rechenberg B, Hofmann-Amtenbrinck M, Schneider E, Muller-Terpitz R, Thiele F, Rippe KP, Grainger DW: Refining animal
models in fracture research: seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use. BMC Musculoskelet Disord 8:72, 2007
3. Biggs MJ, Richards RG, Gadegaard N, Wilkinson CDW, Dalby MJ: Regulation of implant surface
cell adhesion: Characterisation and quantification of S-phase primary osteoblast adhesions on
biomimetic nanoscale substrates. J Orthop Res 25(2):273–282, 2007
4. Biggs MJ, Richards RG, Gadegaard N, Wilkinson CDW, Dalby MJ: The effects of nanoscale pits
on primary human osteoblast adhesion formation and cellular spreading. J Mater Sci Mater
Med 18(2):399–404, 2007
5. Boger A, Heini P, Windolf M, Schneider E: Adjacent vertebral failure after vertebroplasty: a
biomechanical study of low modulus PMMA cement. Eur Spine J 16:2118–2125, 2007
1 The explanted proximal tibiae were
evaluated using micro-computed tomography (µCT40®, SCANCO Medical,
Brüttisellen). The long axis of the screw
was lined orthogonally to the axis of
the X-ray beam to reduce artifacts
induced by the presence of metal (i.e.
titanium) within the scanned volume.
Two hundred and fifty 2-dimensional
transverse cross-section images were
scanned and reconstructed in 1024
x 1024 pixel matrices. Images were
stored in 3-dimensional arrays with an
isotropic voxel size of 16 µm.
2 Effect of surface topography on osseintegration- cancellous bone.
3 Immunostaing using antibody specific
to Laminin on CD34+ selected cells
after 21 days of culture in presence
of PRGF.
4 Illustration of the surgical approach to
the rat tibia. Plate and screws have
applied on the bone.
6. Bonnaire F, Weber A, Boesl O, Eckhardt C, Schwieger K, Linke B: [“Cutting out” in pertrochanteric fractures – problem of osteoporosis?] “Cutting out” bei pertrochantaeren Frakturen – ein
Problem der Osteoporose? Unfallchirurg 110:425–432, 2007
7. Boudrieau RJ, McCarthy RJ, Keating JH, Milz S, Sprecher CM, Kuenzler TP: Finds discrepancy
between studies on canine tibial plateau leveling osteotomy plates. (Letter to the Editor) Am J
Vet Res 68:1139–1140, 2007
8. Braunstein V, Kirchhoff C, Buhmann S, Mutschler W, Biberthaler P: [Bilateral clavicular fractures
occurring at different times: Conservative vs operative therapy using intramedullary nailing – a
case report.] Zweizeitige bilaterale Klavikulafraktur. Konservative vs. operative Therapie mittels
intramedullaerer Osteosynthese – Fallbericht. Orthopaede 36:757–760, 2007
9. Braunstein V, Wiedemann E, Plitz W, Muensterer OJ, Mutschler W, Hinterwimmer S: Operative treatment of greater tuberosity fractures of the humerus – A biomechanical analysis. Clin
Biomech (Bristol, Avon) 22:652–657, 2007
10. Brodt S, Gisep A, Schwieger K, Suhm N, Appelt A: [Solid body augmentation for comminuted
calcaneal fractures: Development and biomechanical testing of a hybrid osteosynthesis technique.]. Unfallchirurg 110(12):1013–1020, 2007
11. Candrian C, Barbero A, Vonwil D, Bonacina E, Miot S, Farhadi J, Wirz D, Dickinson S, Hollander
A, Jakob M, Li Z, Alini M, Heberer M, Martin I: Engineered cartilage generated by nasal chondrocytes is responsive to physical forces resembling joint loading. Arthritis Rheum. 58(1):197–208, 2007
12. Ganser A, Thompson RE, Tami I, Neuhoff D, Steiner A, Ito K: An in vivo experimental comparison of stainless
steel and titanium Schanz screws for external fixation. Eur J Trauma Emerg Surg 33:59–68, 2007
13. Glarner M, Gogolewski S: Degradation and calcification in vitro of new bioresorbable terpolymers of lactides
with an improved degradation pattern. Polymer Degradation Stability 92:310–326, 2007
14. Gogolewski S, Gorna K: Biodegradable polyurethane cancellous bone graft substitutes in the treatment of iliac
crest defects. J Biomed Mater Res A 80-A:94–101, 2007
15. Grant JA, Bishop NE, Gotzen N, Sprecher C, Honl M, Morlock MM: Artificial composite bone as a model of human trabecular bone: The implant-bone interface. J Biomech 40:1158–1164, 2007
16. Gugala Z, Lindsey RW, Gogolewski S: New approaches in the treatment of critical-size segmental defects in long
bones. Macromol Symp 253:147–161, 2007
17. Hammer TO, Wieling R, Green JM, Suedkamp NP, Schneider E, Mueller CA: Effect of re-implanted particles from
intramedullary reaming on mechanical properties and callus formation. A laboratory study. J Bone Joint Surg Br
89:1534–1538, 2007
18. Harris LG, Meredith DO, Eschbach L, Richards RG: Staphylococcus aureus adhesion to standard micro-rough
and electropolished implant materials. J Mater Sci Mater Med 18(6):1151–1156, 2007
19. Hill CM, An YH, Kang QK, Hartsock LA, Gogolewski S, Gorna K: Osteogenesis of osteoblast-seeded polyurethane-hydroxyapatite scaffolds in nude mice. Macromol Symp 253:94–97, 2007
20. Huber G, Morlock MM, Ito K: Consistent hydration of intervertebral discs during in vitro testing. Med Eng Phys
29:808–813, 2007
21. Ip WY, Gogolewski S: Clinical application of resorbable polymers in guided bone regeneration. Macromol Symp
253:139–146, 2007
22. Isaksson H, Comas O, Van Donkelaar CC, Mediavilla J, Wilson W, Huiskes R, Ito K: Bone regeneration during distraction osteogenesis: Mechano-regulation by shear strain and fluid velocity. J Biomech 40:2002–2011, 2007
23. Jones M, Gantenbein B, Fet V, Blaxter M: The effect of model choice on phylogenetic inference using mitochondrial sequence data: lessons from the scorpions. Mol Phylogenet Evol 43:583–595, 2007
24. Kaelicke T, Koller M, Frangen TM, Schlegel U, Sprutacz O, Printzen G, Muhr G, Arens S: Local application of basic
fibroblast growth factor increases the risk of local infection after trauma: an in-vitro and in-vivo study in rats.
Acta Orthop 78(1):63–73, 2007
25. Kirchhoff C, Braunstein V, Buhmann S, Kanz KG, Mutschler W, Biberthaler P: [Traumatic posterior shoulder
dislocation : Diagnosis and therapy.] Diagnostik und Behandlungsregime der traumatischen dorsalen Schulterluxation. Unfallchirurg 110(12):1059–1064, 2007
26. Klopfenstein Bregger MD, Schawalder P, Rahn B, Eckhardt C, Schneider E, Lill C: Optimization of corticosteroid
induced osteoporosis in ovariectomized sheep: A bone histomorphometric study. Vet Comp Orthop Traumatol
20:18–23, 2007
27. Knothe Tate ML, Ritzman TF, Schneider E, Knothe UR: Testing of a new one-stage bone-transport surgical procedure exploiting the periosteum for the repair of long-bone defects. J Bone Joint Surg Am 89:307–316, 2007
28. Krause F, Windolf M, Schwieger K, Weber M: Ankle joint pressure in pes cavovarus. J Bone Joint Surg Br
89:1660–1665, 2007
29. Lee C, Alini M: The development of an in vitro intervertebral disc organ culture system. Altex 24:88–90, 2007
30. Lee CR, Sakai D, Nakai T, Toyama K, Mochida J, Alini M, Grad S: A phenotypic comparison of intervertebral disc
and articular cartilage cells in the rat. Eur Spine J 16(12):2174–2185, 2007
31. Li Z, Yao S, Alini M, Grad S: Different response of articular chondrocyte subpopulations to surface motion. Osteoarthritis Cartilage 15(9):1034–1041, 2007
32. Mastrogiacomo M, Papadimitropoulos A, Cedola A, Peyrin F, Giannoni P, Pearce SG, Alini M, Giannini C, Guagliardi A, Cancedda R: Engineering of bone using bone marrow stromal cells and a silicon-stabilized tricalcium
phosphate bioceramic: Evidence for a coupling between bone formation and scaffold resorption. Biomaterials
28:1376–1384, 2007
33. Meredith DO, Riehle MO, Curtis AS, Richards RG: Is surface chemical composition important for orthopaedic
implant materials? J Mater Sci Mater Med 18(2):405–413, 2007
34. Meredith DO, Eschbach L, Riehle MO, Curtis AS, Richards RG: Microtopography of metal surfaces influence
fibroblast growth by modifying cell shape, cytoskeleton and adhesion. J Orthop Res 25(11):1523–1533, 2007
35. Milz S, Sicking B, Sprecher CM, Putz R, Benjamin M: An immunohistochemical study of the triangular fibrocartilage complex of the wrist: regional variations in cartilage phenotype. J Anat 211:1–7, 2007
36. Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG: Animal models for implant biomaterial research in bone:
A review. Eur Cell Mater 13:1–10, 2007
37. Richards RG, Simpson AE, Jaehn K, Furlong PI, Stoddart MJ: Establishing a 3D ex vivo culture system for investigations of bone metabolism and biomaterial interactions. Altex 24:55–59, 2007
38. Schlickewei C, Verrier S, Lippross S, Pearce S, Alini M, Gogolewski S: Interaction of sheep bone marrow stromal
cells with biodegradable polyurethane bone substitutes. Macromol Symp 253:162–171, 2007
39. Schupp W, Arzdorf M, Linke B, Gutwald R: Biomechanical testing of different osteosynthesis systems for segmental resection of the mandible. J Oral Maxillofac Surg 65(5):924–930, 2007
40. Seitz S, Ern K, Lamper G, Docheva D, Drosse I, Milz S, Mutschler W, Schieker M: Influence of in vitro cultivation
on the integration of cell-matrix constructs after subcutaneous implantation. Tissue Eng 13:1059–1067, 2007
41. Seller K, Wahl D, Wild A, Krauspe R, Schneider E, Linke B: Pullout strength of anterior spinal instrumentation: a
product comparison of seven screws in calf vertebral bodies. Eur Spine J 16:1047–1054, 2007
42. Sigrist IM, Gerhardt C, Alini M, Schneider E, Egermann M: The long-term effects of ovariectomy on bone metabolism in sheep. J Bone Miner Metab 25:28–35, 2007
43. Suhm N, Hengg C, Schwyn R, Windolf M, Quarz V, Haenni M: Mechanical torque measurement predicts load
to implant cut-out: a biomechanical study investigating DHS anchorage in femoral heads. Arch Orthop Trauma
Surg 127(6):469–474, 2007
44. Thiele OC, Eckhardt C, Linke B, Schneider E, Lill CA: Factors affecting the stability of screws in human cortical
osteoporotic bone. A cadaver study. J Bone Joint Surg Br 89(5):701–705, 2007
45. Tischer T, Vogt S, Aryee S, Steinhauser E, Adamczyk C, Milz S, Martinek V, Imhoff AB: Tissue engineering of the
anterior cruciate ligament: a new method using acellularized tendon allografts and autologous fibroblasts. Arch
Orthop Trauma Surg 127:735–741, 2007
46. Van der Werf M, Lezuo P, Maissen O, Van Donkelaar C, Ito K: Inhibition of vertebral endplate perfusion results in
decreased intervertebral disc intranuclear diffusive transport. J Anat 211(6):769–774, 2007
47. Von Knoch F, Eckhardt C, Alabre CI, Schneider E, Rubash HE, Shanbhag AS: Anabolic effects of bisphosphonates
on peri-implant bone stock. Biomaterials 28:3549–3559, 2007
48. Weinberg AM, Castellani C, Arzdorf M, Schneider E, Gasser B, Linke B: Osteosynthesis of supracondylar humerus fractures in children: A biomechanical comparison of four techniques. Clin Biomech (Bristol, Avon)
22:502–509, 2007
Book Chapters
1. Alini M, Ito K, Nerlich AG, Boos N: Aging and pathological degeneration – Biology of the spine. In: AO Spine
Manual – Principles and Techniques, Vol 1, pp 86–100. Ed by M Aebi, V Arlet, and JK Webb. AO Publishing,
2007
2. Giannoudis PV, Schneider E: Osteoporosis. In: AO Principles of Fracture Management – Volume 1 - Principles
– Second expanded edition pp 468–481. Ed by TP Ruedi, RE Buckley, and CG Moran. AO Publishing – Thieme:
Stuttgart, New York, 2007
3. Ito K, Perren SM: Biology and biomechanics in bone healing. In: AO Principles of Fracture Management
– Volume 1 - Principles – Second expanded edition pp 8–31. Ed by TP Ruedi, RE Buckley, and CG Moran. AO
Publishing – Thieme: Stuttgart, New York, 2007
4. Messmer P, Perren SM, Suhm N: Screws. In: AO Principles of Fracture Management – Volume 1 - Principles
– Second expanded edition pp 213–225. Ed by TP Ruedi, RE Buckley, and CG Moran. AO Publishing – Thieme:
Stuttgart, New York, 2007
5. Richards RG, Perren SM: Implants and materials in fracture fixation. In: AO Principles of Fracture Management
– Volume 1 - Principles – Second expanded edition pp 32–44. Ed by TP Ruedi, RE Buckley, and CG Moran. AO
Publishing – Thieme: Stuttgart, New York, 2007
Habilitations
1. Kunz C. Distraction osteogenesis of the canine mandible – Manipulation of shape after linear distraction. Experimental study to enhance precision of three-dimensional distraction osteogenesis of the craniomaxillofacial
skeleton. 1–120. 2007. Universitaetsklinik fuer Wiederherstellende Chirurgie, Abteilung fuer Kiefer- und
Gesichtschirurgie, Basel, Switzerland. (B. Rahn)
Dissertations
1. Aktas T. Die molekulare Zusammensetzung der extrazellulären Matrix des Lig. scapholunatum. 1–64. 2007.
Anatomische Anstalt, Ludwig-Maximilians-Universität München, Germany.
Dr. med. (S. Milz)
2. Denom J. Etude de l‘influence de diverses proportions cellulaires sur la différenciation des cellules HUVEC et
hBMSC - Rapport de stage. 1–64. 2007. University of Evry, France.
MSc. (S. Verrier, M. Alini)
3. Griffon S. Preparation of a composite carrier for the tissue engineering of cartilage. 2007. University of Evry,
France. MSc. (D. Eglin, M. Alini)
4. Isaksson HE. Mechanical and mechanobiological influences on bone fracture repair - identifying important cellular characteristics. 1–167. 2007. Eindhoven Technical University, The Netherlands. PhD. (K. Ito)
5. Jakob J. Die molekulare Zusammensetzung der extrazellulären Matrix im Lig. coracoacromiale. 1–72. 2007.
Anatomische Anstalt, Ludwig-Maximilians-Universität München, Germany.
Dr. med. (S. Milz)
6. Leitner M. Comparison of locking and conventional screws on tibial plateau positioning and biomechanical
stability after TPLO plate fixation. 1–39. 2007. Vetsuisse-Fakultaet, Departement fuer klinische Veterinaermedizin
Abteilung Chirurgie und Orthopaedie, University of Bern, Switzerland. Dr. med. vet. (S. Pearce, P. Schawalder)
7. Pucher MM. Longitudinal pQCT measurements can be used to evaluate bone loss in the ovariectomised rat
model avoiding the use of sham animals. 1–24. 2007. Vetsuisse-Fakultät, Departement für Kleintiere, Klinik für
Kleintierchirurgie, University of Zurich, Switzerland.
Dr. med. vet. (K. Ito, P. Montavon)
8. Rey K. Knochenreaktion nach Osteosynthese mit einer Kohlenstofffasser-PEEK Platte. 1–71. 2007. Dr. med.
Julius-Maximilian-Universität Würzburg, Germany. (C. Hendrich, R.H. Meffert, B. Rahn)
9. Schlegel U. The composite structure of cactus spines and their potential for the construction of implants in
orthopaedics and traumatology. 1–152. 2007. Institute of Biological Sciences, University of Wales, Aberystwyth,
Great Britain. PhD. (I ap Gwynn)
10. Seebeck J. Mechanik der Osteosynthese von proximalen Tibiafrakturen durch einen internen Fixateur unter
Beruecksichtigung altersbedingter Knochenveraenderungen. 1–174, 2007. Technische Universitaet HamburgHarburg, Germany. Dr.-Ing. (E. Schneider, DG. Feldmann, MM. Morlock)
11. Sicking B.C. Molekulare Zusammensetzung der extrazellulären Matrix im Discus articularis ulnae und im Meniscus ulnocarpalis des Menschen. 1–80. 2007. Anatomische Anstalt, Ludwig-Maximilians-Universität München,
Germany. Dr. med. (S. Milz)
12. Sigrist I. The long-term effects of ovariectomy on bone metabolism in sheep. 1–31. 2007. Musculoskeletal
Research Unit (MSRU), Pferdeklinik, Vetsuisse-Fakultaet, University of Zurich, Switzerland. Dr. med. vet. (M.
Egermann, B. von Rechenberg, E. Schneider)
13. Thiele OC. Einflüsse der Strukturveränderung von osteoporotischer humaner Kortikalis auf die Implantatstabilität. 1–104. 2007. Ruprecht-Karls-Universität Heidelberg, Germany.
Dr. med. (CA. Lill, F. Resch)
14. Troester SC. Auswirkungen einer intrazerebralen Applikation von Leptin auf die mechanischen Eigenschaften
des Knochens beim Schaf. 1–75. 2007. Pferdeklinik University of Zurich, Switzerland. Dr. med. (J. Auer, E. Schneider)
15. Unterer N. Verteilung von Abriebpartikeln von Titan und Stahl in verschiedene Organe. Eine vergleichende in
vivo Studie. 1–96. 2007. Ludwig-Maximilian-Universität zu München,
Germany. Dr. med. (W. Plitz, W. Gernet, M. Graw, M.A. Wimmer, B. Rahn)
16. Voisard MX. Comparison of soft tissue reactions to titanium CP, Ti-6Al-7Nb, Ti-15Mo and stainless steel with
various surface characteristics in an in vivo model. 1–120. 2007. Klinik Orthopaedische Chirurgie, University of
Bern, Switzerland. Dr. med. (B. Rahn)
17. Welton JL. In vivo evaluation of defined polished surfaces to prevent soft tissue adhesion.
1–115. 2007. Institute of Biological Sciences, The University of Wales, Aberystwyth, Wales, Great Britain. M.Phil
(R.G. Richards, I ap Gwynn).
8. Presentations
Presentations (with published abstracts)
1. Egermann M, Lill CA, Ito K, Schneider E: Animal models for fracture treatment in osteoporosis: Induction of
bone loss in sheep. Eur Cell Mater 14 S1:60, 2007
2. Egermann M, Heil P, Groengroeft I, Ito K, Hofstetter W, Richards P: Fracture healing in a mouse model for senile
osteoporosis. Eur Cell Mater 14 S1:4, 2007
3. Ferguson S, Alini M, Boos N, Ito K, McNally D, Steffen T, Cheung K: AO spine research network: Global collaboration to address disc degeneration and regeneration. Eur Cell Mater 13 S2:21, 2007
4. Gantenbein-Ritter B, Juenger S, Chan S, Alini M, Ito K: Whole disc organ culture: Analyzing possible causes of
disc degeneration and regenerative approaches. Eur Spine J 16:1712, 2007
5. Grad S, Alini M: Looking for specific molecular markers for the intervertebral disc. Eur Spine J 16:1713, 2007
6. Hayes JS, Archer CW, Richards RG: In vitro effect of surface polishing for reducing bony overgrowth. Eur Cell
Mater 13 S3:9, 2007
7. Hayes JS, Archer CW, Richards RG: Controlling hard tissue integration at the bone-implant interface. Eur Cell
Mater 13 S2:67, 2007
8. Hayes JS, Archer C, Richards RG: Implant osseointegration: in vitro analysis of titanium microtopography. Eur Cell
Mater 14 S1:20, 2007
9. Iatridis JC, MacLean JJ, Roughley PJ, Alini M: Intervertebral disc mechanobiology and the kinetics of gene expression. Eur Cell Mater 13 S2:25, 2007
10. Ito K, Van Oosterwyck H, Haas C, Gantenbein B, Zeiter S: Mechanoregulation of cell phenotype for musculoskeletal tissue engineering. Eur Cell Mater 13 S2:34, 2007
11. Jaehn K, Stoddart MJ, Furlong PI, Archer CW, Richards RG: Viability and procollagen-I expression of cultured
human cancellous bone explants using a serum free medium containing TGF-Beta3. Eur Cell Mater 14 S1:41,
2007
12. Jaehn K, Stoddart MJ, Furlong PI, Jones DB, Archer CW, Richards RG: Effect of a serum free medium containing
TGF-ß3 on osteocyte viability of cultured human cancellous bone explants. Eur Cell Mater 13 S3:13, 2007
13. Jones DB, Noble B, Vico L, VanderSloten J, Martin I, Richards RG: Bioreactors for tissue engineering scaffolds
and ex vivo tissues. ELGRA News 25:106–107, 2007
14. Leitner M, Pearce S, Windolf M, Zeiter S, Schawalder P, Johnson K: Evaluation of tibia plateau positioning and
biomechanical stability of TPLO plate fixation using either locking or conventional screws. Vet Surg 36:E15, 2007
15. Lippross S, Verrier S, Benneker LM, Alini M: Platelet released growth factors boost expansion of endothelial
progenitor cells. Eur Cell Mater 14 S1:34, 2007
16. Maddikeri RR, Tosatti S, Textor M, Richards RG, Harris LG: Bacterial adhesion to PLL-g-PEG modified surfaces. Eur
Cell Mater 13 S2:70, 2007
17. Mastrogiacomo M, Papadimitropoulos A, Cedola A, Peyrin F, Giannoni P, Pearce SG, Alini M, Giannini C, Guagliardi A, Cancedda R: Evidence for a coupling between bone formation and scaffold resorption in an engineering scaffold of tricalcium phosphate bioceramic and bone marrow stromal cells. Tissue Eng 13:1691–1692,
2007
18. Meredith DO, Harris LG, Riehle MO, Curtis AS, Richards RG: Effect of metal implant surface topography on
fibroblast behaviour and bacterial adhesion. Eur Cell Mater 13 S2:77, 2007
19. Milz S: Tissue reaction around implants – the histological view. Eur Cell Mater 14 S1:43, 2007
20. Niemeyer P, Vohrer J, Kloeppel H, Milz S, Schoenberger T, Suedkamp NP, Schneider E, Pearce S: HLA-independent use of mesenchymal stem cells for regeneration of bone: Preliminary results of a critical size defect study
in the sheep tibia. Eur Cell Mater 14 S1:14, 2007
21. Pearce AI, Pearce SG, Milz S, Archer CW, Richards RG: In vivo evaluation of cpTi and TAN screws with modified
surfaces to reduce bony integration. Eur Cell Mater 13 S2:75, 2007
22. Pearce SG: Animal models for bone repair. Eur Cell Mater 14 S1:42, 2007
23. Perren SM: State of the art and future of bone repair. Eur Cell Mater 14 S1:47, 2007
24. Pioletti DP, Laurent-Applegate L, Zambelli PY, Ito K: Treatment of non-union fractures with fetal cell therapy. Eur
25. Richards RG: Implant surfaces in fracture fixation: In vitro & in vivo. Eur Cell Mater 14 S1:44, 2007
26. Richards RG: Surfaces to control implant tissue adhesion for osteosynthesis. Reynders, P., Burssens, P., Bellemans, J., and Broos, P. Folia Traumatologica Lovaniensia 15, 2007.
27. Salzmann GM, Schmitz P, Anton M, Stoddart M, Grad S, Milz S, Tischer T, Vogt S, Gansbacher B, Imhoff AB, Alini
M: The combination of dynamic compression and shear with rvBMP-2 for in-vitro cartilage tissue engineering.
Osteoarthritis and Cartilage 15 S2:B81, 2007
28. Schonberger T, Hahn J, Kasten P, Suedkamp NP, Fechner K, Pearce S, Niemeyer P: A novel software-based
evaluation method for objective quantification of bone regeneration in experimental bone defects. Eur Cell
Mater 14 S1:92, 2007
29. Seebach C, Henrich D, Scherzed A, Alini M, Marzi I: “Early” endothelial progenitor cells (EPC) on beta-Tricalcium
Phosphate scaffold under osteogenic conditions are useful for vascularisation in bone tissue engineering. Eur
30. Stoddart MJ, Simpson AE, Furlong PI, Davies CM, Jones DB, Richards RG: Mechanically loaded ex vivo culture
system for cancellous bone biopsies. Eur Cell Mater 13 S2:68, 2007
31. Stoddart MJ, Furlong PI, Simpson AE, Davies CM, Richards RG: Viability in ex vivo cultured cancellous bone. Eur
32. Terhorst S, Landes CA, Sader R, Benjamin M, Milz S: Extracellular matrix molecules in the lateral ligament of the
human temporomandibular joint. Int J Oral Maxillofacial Surg 36:1110, 2007
33. Verrier S, Meury T, Lippross S, Alini M: An engineered vascularized graft for large bone defect. Eur Cell Mater 13
S2:38, 2007
34. Verrier S, Lippross S, Hoppe S, Schlickewei C, Alini M: Integration of sheep peripheral vein endothelial cells into
polyurethane scaffolds-delivering angiogenic potential into autologous graft constructs. Eur Cell Mater 14 S1:35,
2007
35. Viehoefer A, Buettner A, Boszczyk A, Boszczyk BM, Benjamin M, Milz S: The molecular composition of the extracellular matrix of the human iliolumbar ligament. Eur Spine J 16 S1:82–83, 2007
36. Wegener B, Bergschmidt P, Milz S, Jansson V, Muller PE: Influence of matrix-based microfracture on the therapy
of chondral defects in an animal model. Osteoarthritis and Cartilage 15 S2:B85, 2007
37. Wimmer MA, Goerke UJ, Grad S, Alini M, Guenther H: Numerical simulation of functional tissue engineering for
articular cartilage. Eur Cell Mater 13 S2:13, 2007
38. Windolf M, Leitner M, Schwieger K, Pearce S, Schneider E, Johnson K: The biomechanical consequences of the
TPLO procedure. Vet Surg 36:E28, 2007
Presentations (with non-published abstracts)
39. Alini M, Stoddart M: Use of mesenchymal stem cells for bone tissue engineering: present limitations. The 4th
Swiss Stem Cell Network Meeting. Zurich, Switzerland, 2007
40. Biggs MJP, Richards RG, Gadegaard N, Wilkinson CDW, Dalby MJ: The influence of nanoscale biomimetic
structures on osteoblast adhesion. Annual Meeting Society for Experimental Biology SEB, Glasgow, Great Britain,
2007
41. Biggs MJP, Richards RG, Gadegaard N, Wilkinson CDW, Oreffo RO, Dalby MJ: The influence of nanoscale topography on osteoblast adhesion and genetic expression. TERMIS, Toronto, Canada, 2007
42. Boger A, Heini P, Windolf M, Schneider E: Can the decrease in failure strength due to augmentation of functional spine units be avoided using low modulus bone cement? Society for Biomaterials, Chicago IL, USA, 2007
43. Boudrieau RJ, McCarthy RJ, Sprecher CM, Kuenzler TP, Keating JH, Milz S: Material properties and tissue reaction
of the Slocum TPLO plate. American Society for Testing of Materials ASTM F04 – Workshop on Metallic Corrosion of Small Implants, Norfolk VA, USA, 2007
44. Bouré LP, Zeiter S, Seidenglanz U, Leitner M, Van der Pol B, Matthys R, Schneider E, Pearce SG: A novel sheep
model for evaluating biomaterials in cancellous bone. 21st Conference European Society for Biomaterials ESB,
Brighton, Great Britain, 2007
45. Braunstein V: A new method for the definition of glenoid version: The fulcrum axis. 10th International Congress
on Surgery of the Shoulder ICSS, Costa do Sauipe, Brazil, 2007
46. Braunstein V: Conclusions cannot be drawn for fresh-frozen humeral heads from those that are embalmed,
after biomechanical load-to-failure tests. 10th International Congress on Surgery of the Shoulder ICSS, Costa do
Sauipe, Brazil, 2007
47. Braunstein V: Die Klavikulafraktur beim Sportler: offene vs. minimalinvasive operative Therapie. 9. Münchner
Sporttaumatologie-Tage, Munich, Germany, 2007
48. Braunstein V: Eine neue Methode zur Bestimmung der Glenoid Version: Die Fulcrum-Achse. 71. Jahrestagung
Deutsche Gesellschaft für Unfallchirurgie DGU, Berlin, Germany, 2007
49. Braunstein V: Eine neue Methode zur Bestimmung der Retroversion des Glenoids: Die Fulcrum-Achse. 14.
Jahrestagung der Deutschen Vereinigung für Schulter- und Ellenbogenchirurgie DVSE, Münster, Germany, 2007
50. Braunstein V: Hochgradige Rotatorenmanschettenrupturen: Refixation oder Debridement? Kurz-, mittel- und
langfristige Ergebnisse. Arthroskopiekurs Nürnberg, Germany, 2007
51. Braunstein V: Refixation is superior to debridement in case of rotator cuff lesions grade 3: A long-term study.
10th International Congress on Surgery of the Shoulder ICSS, Costa do Sauipe, Brazil, 2007
52. Braunstein V: Time-shifted bilateral clavicular fracture: Conservative vs. operative therapy using intramedullary
nailing – A Case Report. 10th International Congress on Surgery of the Shoulder ICSS, Costa do Sauipe, Brazil,
2007
53. Braunstein V: Treatment of forearm shaft fractures. AO Advanced Shoulder and Upper Limb Course; Johannesburg, South Africa, 2007
54. Candrian C, Vonwil D, Barbero A, Bonacina E, Farhadi J, Miot S, Wolf F, Wirz D, Daniels A, Dickinson S, Hollander
A, Alini M, Jakob M, Martin I, Heberer M: Tissue engineered nasal cartilage is responsive to joint specific physical
forces. 13th Annual ESA Meeting, Zurich, Switzerland, 2007
55. Chan SC, Gantenbein B, Chan D, Lu W, Cheung K, Lezuo P, Ito K: Fate of mesenchymal stem cells injected into
intervertebral discs. International Society for the Study of the Lumbar Spine ISSLS, Hong Kong, HK, 2007
56. Demers CN, Michalek AJ, Iatridis JC, Goswami T, Beaudoin G, Beckman L, Alini M, Mwale F, Antoniou J: Assessing T1rho-weighted MR imaging in relation to the biochemical and mechanical properties of trypsin-treated
intervertebral discs. ORS, San Diego 2007
57. Egermann M, Ito K, Hofstetter W, Wanner GA, Richards P: Frakturheilung in einem Tiermodell fuer senile Oseteoporose (SAMP6-Maus). 71. Jahrestagung Deutsche Gesellschaft für Unfallchirurgie DGU, Berlin, Germany,
2007
58. Eglin D, Alini M: Biocompatibility – Cell material interaction in Tissue Engineering. Symposium on Stem Cell and
Tissue Engineering in Plastic, Reconstructive and Aesthetic Surgery, Samsun, Turkey, 2007
59. Eglin D, Glarner M, Alini M, Gogolewski S: Biodegradable linear polyurethane scaffold incorporating isoprenoid
alcohol. 7th International Symposium on Frontiers in Biomedical Polymers. Ghent, Belgium, 2007
60. Eglin D, Grad S, Griffon S, Alini M: A hyaluronan biodegradable poly(urethane) scaffold for cartilage tissue engineering construct. Biologic Scaffolds for Regenerative Medicine: Fifth Symposium, Phoenix (US), 2007
61. Eglin D, Tsui YK, Glarner M, Alini M: Polyurethane bi-phasic construct for osteochondral defect repair. Euromat
2007 Conference, Nurnberg, Germany, 2007
62. Fritscher KD, Schuler B, Gruenerb A, Haenni M, Suhm N, Schwieger K, Schubert R: Assessment of femoral bone
quality using co-occurrence matrices and adaptive regions of interest. SPIE Medical Imaging, San Diego 2007
63. Gantenbein B, Ito K: Verfrühte Bandscheibendegeneration beim Menschen – Ursachenanalyse aus dem Reagenzglas. Academia Raetica Symposium, Chur, Switzerland, 2007
64. Grad S, Sakai D, Nakai T, Lee CR, Mochida J, Alini M: Immunolocalization of annexin a3, pleiotrophin, and matrix
gla protein in rat intervertebral disc. ISSLS Annual Meeting, Hong Kong, HK, 2007
65. Grad S, Wernike E, Alini M: Effects of reduced oxygen tension and long-term mechanical stimulation on chondrocytes-polymer constructs. 7th World Congress of the ICRS, Warsaw, Poland, 2007
66. Grad S, Wimmer MA, Peter R, Alini M: The effect of articular motion on chondrocytes in 3D scaffolds depends
on the relative velocity. 53rd Annual ORS, San Diego CA, USA, 2007
67. Groengroeft I, Heil P, Matthys-Mark R, Lezuo P, Tami A, Perren S, Montavon P, Ito K: Fixation compliance in a
murine fracture model induces two different processes of fracture healing but does not lead to delayed union.
6th Combined ORS, Honolulu HI, USA, 2007
68. Hahn J, Milz S, Pearce A, Schawalder P, Gruner H, Schneider E, Wieling R, Pearce S: Titanium VPS coating to
increase bone ongrowth of endless carbon fibre PEEK implants. 21st Conference European Society for Biomaterials ESB, Brighton, Great Britain, 2007
69. Hayes JS, Archer CW, Richards RG: In vitro effects of surface polishing on osteoblast behaviour - Potential for reducing extraosseous formation for implant retrieval. 13th Annual Meeting Swiss Bone and Mineral Society SBMS,
Zurich 2007
70. Hayes JS, Archer CW, Richards RG: Reducing bone encasement of metal implants for elective removal. 53rd Annual ORS, San Diego CA, USA, 2007
71. Hayes JS, Archer CW, Richards RG: The potential of surface polishing for elective internal fixator retrieval. 21st
Conference European Society for Biomaterials ESB, Brighton, Great Britain, 2007
72. Isaksson H, Groengroeft I, Wilson W, Van Donkelaar CC, Huiskes R, Ito K: Dual cortex formation during fracture
callus remodeling in mice can be explained by mechanical loading mode. Summer Workshop European Society
of Biomechanics ESB, Dublin, Ireland, 2007
73. Isaksson H, Groengroeft I, Wilson W, Van Donkelaar CC, Van Rietbergen B, Tami A, Huiskes R, Ito K: Remodeling
of fracture callus in mice can be explained by mechanical loading. ASME Summer Bioengineering Conference,
Keystone CO, USA, 2007
74. Isaksson H, Van Donkelaar CC, Huiskes R, Ito K: Importance of including cell phenotype specific activities when
modeling tissue differentiation and bone healing. Summer Workshop European Society of Biomechanics ESB,
Dublin, Ireland, 2007
75. Isenberg J, Pearce S, Milz S, Radtke R, Schneider E, Rehm KE: Gefaessdestruktion und Neoangiogenese im kritischen Segmentdefekt. 71. Jahrestagung Deutsche Gesellschaft für Unfallchirurgie DGU, Berlin, Germany, 2007
76. Isenberg J, Rehm KE, Kluge K, Tami A, Milz S, Pearce S: Die winkelstabil fixierte Marknagelung – neue Aspekte
im Großtiermodel. 71. Jahrestagung Deutsche Gesellschaft für Unfallchirurgie DGU, Berlin, Germany, 2007
77. Jaehn K, Stoddart M, Furlong PI, Archer CW, Richards RG: Effect of serum free medium on osteocyte viability in
ex vivo cultured human cancellous bone explants. 13th Annual Meeting Swiss Bone and Mineral Society SBMS,
Zurich, Switzerland, 2007
78. Jaehn K, Stoddart MJ, Furlong PI, Archer CW, Richards RG: Osteocyte viability and influence of culture conditions
on ex vivo human cancellous bone. 21st Conference European Society for Biomaterials ESB, Brighton, Great
Britain, 2007
79. Juenger S, Gantenbein B, Lezuo P, Ferguson SJ, Ito K: Effect of limited nutrition on in situ intervertebral disc cells
under “physiological” loading. International Society of the Lumbar Spine ISSLS, Hong Kong, HK, 2007
80. Kluge K, Larenza MP, Pearce SG, Bettschart-Wolfensberger R: Femoral and sciatic nerve electrolocation and
desensitization with lidocaine and bupivacaine in rabbits undergoing stifle joint arthrotomy. AVA/ECVAA, Leipzig
2007
81. Kubosch D, Milz S, Bley TA, Sprecher CM, Suedkamp NP, Strohm PC: Die Diagnose des Transplantatversagens
bei der ventralen lumbalen Spondylodese: Eine Frage der Aufloesung, demonstriert am Xtreme-CT. 71. Jahrestagung Deutsche Gesellschaft für Unfallchirurgie DGU, Berlin, Germany, 2007
82. Kupcsik L, Meury T, Flury M, Alini M: In vitro effect of statins on human bone marrow stromal cells. 53rd Annual
ORS, San Diego CA, USA, 2007
83. Kupcsik L, Stoddart M, Alini M: Mechanical stimulation alters gene expression of human mesenchymal stem
cells. 6th Combined ORS, Honolulu HI, USA, 2007
84. Lippross S, Verrier S, Alini M: Platelet released growth factors boost expansion of endothelial progenitor cells.
13th Annual Meeting Swiss Bone and Mineral Society SBMS, Zurich, Switzerland, 2007
85. Lippross S, Verrier S, Hoffmann A, Alini M: Platelet released growth factors boost expansion of endothelial progenitor cells. 53rd Annual ORS, San Diego CA, USA 2007
86. Milz S: Bone biology, bone healing with special reference to the CMF skeleton. AO Craniomaxillofacial Principles
Course, Davos, Switzerland, 2007
87. Milz S: Heilt der Knorpel? Autologe Reparationsvorgänge bei Knorpelläsionen. 6. Unfallchirurgisch-Sportorthopädisches Zugspitzsymposium, Knorpel- und Bandrekonstruktionen – Arthrose vermeiden. Garmisch-Partenkirchen, Germany, 2007
88. Müller AM, Davenport M, Alini M, Verrier S, Martin I, Scherberich A: Serum-free expansion of adipose-derived
cells with platelet-derived growth factors. The 4th Swiss Stem Cell Network Meeting, Zurich, Switzerland, 2007
89. Noailly J, Van Oosterwyck H, Wilson W, Ito K: Poroviscoelastic description for fibrin gels. Finite Element Modeling in Biomechanics and Mechanobiology. Summer Workshop European Society of Biomechanics ESB, Dublin,
Ireland, 2007
90. Pearce AI, Pearce SG, Milz S, Archer CW, Richards RG: In vivo evaluation of polished titanium and titanium alloy
screws to minimize bone adhesion. 13th Annual Meeting Swiss Bone and Mineral Society SBMS, Zurich, Switzerland, 2007
91. Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG: Animal models for implant biomaterials research in
bone: Review. 21st Conference European Society for Biomaterials ESB, Brighton, Great Britain, 2007
92. Poser L, Schwieger K, Matthys R, Zeiter S, Schawalder P, Schneider E, Pearce S: Standardized critical size bone
defect model in osteoporotic and non-osteoporotic rats using a new angular stable internal fixator. 6th Combined ORS, Honolulu HI, USA, 2007
93. Poser L, Zeiter S, Schawalder P, Schneider E, Schneider M, Mathys R, Toggwiler P, Pearce S: Critical size defect
model in osteoporotic rats as screening method for new treatment technologies. 13th Annual Meeting Swiss
Bone and Mineral Society SBMS, Zurich, Switzerland, 2007
94. Pucher MM, Tami AE, Mueller TL, Van Lenthe GH, Mueller R, Montavon P, Ito K: The effect of hydroxyapatite
(Endobon) particles on implant osseointegration in osteoporotic trabecular bone. 6th Combined ORS, Honolulu
HI, USA, 2007
95. Richards RG: Bioreactors: Culturing human bone ex vivo. Institute of Biomaterials and Bioengineering, Tokyo
Medical and Dental University, Japan, 2007
96. Richards RG: Bioreactors: Culturing human bone ex vivo. 9th Tooth Morphogenesis and Differentiation Conference, University of Zurich, Switzerland, 2007
97. Richards RG: Can we influence the risk of infection by design changes of the implant? Institute of Biomaterials
and Bioengineering, Tokyo Medical and Dental University, Japan, 2007
98. Richards RG: Can we Influence the risk of infection by design changes of the implant? MEM Research Centre,
Institute for Surgical Technology and Biomechanics. Masters in Biomedical Engineering Program, Bern, Switzerland
99. Richards RG: Control of the implant tissue interface: Role of implant surfaces. AO Craniomaxillofacial Principles
Course. Davos, Switzerland
100. Richards RG: Evolution of plate design and function. AO Principles Course, Davos, Switzerland, 2007
101. Richards RG: From clinical problem to research. AO Educators Seminar for ORP, Davos, Switzerland, 2007
102. Richards RG: Implant Surfaces and Infection. Department. of Orthopaedic Surgery & Musculoskeletal Medicine, Christchurch School of Medicine & Health Sciences, University of Otago, New Zealand, 2007
103. Richards RG: Implant surfaces and infection. European Association for Trauma and Emergency Surgery EATES
joint congress with European Trauma Society ETS, Graz, Austria, 2007
104. Richards RG: Implant surfaces, relevance for the Spine Surgeon. Synthes Inc., Oberdorf, Switzerland, 2007
105. Richards RG: Implant surfaces to help the surgeon. ARI Symposium, Davos, Switzerland, 2007
106. Richards RG: Infection in fracture fixation. Hot Topic Lecture. AO Courses, Davos, Switzerland, 2007
107. Richards RG: Infection in internal fracture fixation. The role of implant surfaces. 15. Arbeitstagung Internationale Arbeitsgemeinschaft Kindertraumatologie, Oberdorf, Switzerland, 2007
108. Richards RG: Infection update. AO Academic Council, Davos, Switzerland, 2007
109. Richards RG: Internal Fracture Fixation: Implant surfaces to reduce bony integration. 15. Arbeitstagung Internationale Arbeitsgemeinschaft Kindertraumatologie, Oberdorf, Switzerland, 2007
110. Richards RG: Jammed locked screws. AO TK Workshop on Implant Removal. Davos, Switzerland, 2007
111. Richards RG: Surfaces to control implant tissue adhesion for osteosynthesis. Institute of Biomaterials and
Bioengineering, Tokyo Medical and Dental University, Japan, 2007
112. Richards RG: Surfaces to control implant tissue adhesion for osteosynthesis MEM Research Centre, Institute
for Surgical Technology and Biomechanics. Masters in Biomedical Engineering Program, Bern, Switzerland,
2007
113. Richards RG: Surfaces to control implant soft and hard tissue adhesion for osteosynthesis: Simple is efficient.
36th Instructional Course, British Orthopaedic Association, 2007
114. Richards RG: Surfaces to control implant tissue adhesion for osteosynthesis. Department. of Orthopaedic
Surgery & Musculoskeletal Medicine, Christchurch School of Medicine & Health Sciences, University of Otago,
New Zealand, 2007
115. Richards RG, Pearce AI, Pearce SG, Milz S, Schneider E, Archer CW: In vivo evaluation of titanium and titanium
alloy screws with modified surfaces to minimize bone adhesion. 53rd Annual ORS, San Diego CA, USA, 2007
116. Richards RG, Welton JL, ap Gwynn I: In vivo evaluation of polished titanium internal fixator surfaces to prevent
soft tissue adhesion. 21st Conference European Society for Biomaterials ESB, Brighton, Great Britain, 2007
117. Rohrbach H, Schwieger K, Guerrero T, Glatt M, Gasser J, Rahn BA: Bone healing under anti-resorptive medication in a canine distal radius model. FELASA-ICLAS, Cernobbio, 2007
118. Sakai D, Grad S, Nakai T, Toyama K, Alini M, Mochida J: Gene expression profiling for appropriate intervertebral
disc regeneration - Differences in large and small animals. 36th Annual Meeting of the Japanese Society for
Spine Surgery and Related Research, Kanazawa, Japan, 2007
119. Salzmann GM, Schmitz P, Anton M, Stoddart M, Grad S, Milz S, Tischer T, Vogt S, Gansbacher B, Imhoff AB, Alini
M: The combination of dynamic compression and shear with rvBMP-2 for in-vitro cartilage tissue engineering.
6th Combined ORS, Honolulu HI, USA, 2007
120. Schneider E: Biology and fixation of fractures. Master Course Biomedical Engineering, University of Bern, Switzerland, 2007
121. Schneider E: CMF projects in histology and tissue morphology. AO CMF Research and Development Committee, Zurich, Switzerland, 2007
122. Schneider E: Concepts of fracture treatment. Master Course Biomedical Engineering, University of Bern, Switzerland, 2007
123. Schneider E: Das AO Forschungsinstitut. Kommission für Bildung und Kultur des Grossen Rates des Kantons
Graubünden, Davos, Switzerland, 2007
124. Schneider E: Die AO Stiftung heute. Master Course Biomedical Engineering, University of Bern, Switzerland,
2007
125. Schneider E: Die AO Stiftung und ihre Forschung. Deutscher Wissenschaftsrat, Davos, Switzerland, 2007
126. Schneider E: From the clinical problem to the publication. 2nd AOLAT Faculty Retreat, Cancun, Mexico, 2007
127. Schneider E: Knochenersatz – Bedeutung unter dem Einfluss von Osteoporose und winkelstabilen Implantaten. 8th AO Course Trauma II Erfurt, Germany, 2007
128. Schneider E: Osteoporose – Forschungsschwerpunkt der AO. 8th AO Course Trauma II, Erfurt, Germany, 2007
129. Schneider E: Praeclinical research projects. 2nd AOLAT Faculty Retreat, Cancun, Mexico, 2007
130. Schneider E: Research and the AO Foundation. CCMX Meeting, Davos, Switzerland, 2007
131. Schneider E: Research and the AO Foundation. Kiwanis Davos-Klosters, Davos, Switzerland, 2007
132. Schneider E: Research in Davos. European Cells and Materials Conference ECM VIII: Bone Tissue Engineering,
Davos, Switzerland, 2007
133. Schneider E: Research – Strategy, Priorities, Results. AO Foundation Trustee Meeting, Beijing, China, 2007
134. Schneider E: Research – What you need to know. Faculty Precourse AO Courses Davos, Switzerland, 2007
135. Schneider E: Road Map of Research. From the clinical problem to publication. AO Courses, Davos, Switzerland
136. Schneider E: Strategic collaboration in osteoporosis – research aspects. AO Academic Council Meeting, Zurich,
Switzerland, 2007
137. Schneider E: Veränderungen in der Frakturbehandlung. Master Course Biomedical Engineering, University of
Bern, Switzerland, 2007
138. Schneider E: Von der Idee zum Medizinprodukt. 71. Jahrestagung Deutsche Gesellschaft für Unfallchirurgie
DGU, Berlin, Germany, 2007
139. Schneider E: Zukunft des Forschungsplatzes Davos. Podium Science City Davos, Switzerland, 2007
140. Schwenke T, Honl M, Schneider E, Galante JO, Jacobs JJ, Wimmer MA: Wear area size is associated with joint
moments and surgical positioning in TKR. ORS, San Diego CA, USA, 2007
141. Schwieger K: Biomechanical investigations of new implant developments. ARI Symposium, Davos, Switzerland, 2007
142. Schwieger K: Design of biomechanical devices. MEM Research Centre, Institute for Surgical Technology and
Biomechanics. Masters in Biomedical Engineering Program, University of Bern, Switzerland, 2007
143. Schwieger K: From research development to product. AO Educators Seminar for ORP, Davos, Switzerland,
2007
144. Schwieger K, Albrecht D, Gueorguiev B, Linke B, Hoentzsch D: Osteosynthesestabilitaet und Versagensmodus
bei der Marknagelung von distalen Tibiaschaftfrakturen mit winkelstabiler und konventioneller Verriegelung
– eine in vitro Studie. 71. Jahrestagung Deutsche Gesellschaft für Unfallchirurgie DGU, Berlin, Germany, 2007
145. Schwieger K, Schneider E, Perren S, Radtke R: Erhoeht die Angulierung von Schrauben die maximale Auszugskraft bei winkelstabilen Schrauben-Platten-Konstrukten? 71. Jahrestagung Deutsche Gesellschaft für Unfallchirurgie DGU, Berlin, Germany, 2007
146. Stoddart M, Chen Y, Alini M: Signalling between chondrocytes from different zones in cartilage. TERMIS, London, UK, 2007
147. Terhorst S, Landes C, Sader R, Benjamin M, Milz S: Die molekulare Zusammensetzung der extrazellulaeren
Matrix im Ligamentum laterale des humanen Kiefergelenkes. Oesterreichische Gesellschaft für Mund-, Kieferund Gesichtschirurgie OEGMKG , Davos, Switzerland, 2007
148. Van der Werf MJ, Zeiter S, Groengroeft ID, Lezuo P, Ito K: The response of nucleus pulposus cells to decreased
diffusion in ovine lumbar spine – Poster Presentation. International Society of the Lumbar Spine ISSLS, Hong
Kong, HK, 2007
149. Verrier S, Lipross S, Hope S, Eglin D, Alini M: Endothelialized bone graft for large bone defects. Symposium on
Stem Cell and Tissue Engineering in Plastic, Reconstructive and Aesthetic Surgery, Samsun, Turkey, 2007
150. Windolf M, Dutoit C, Schwieger K: Stabilitaet und Cut-out Verhalten der DHS-Klinge im Vergleich zur konventionellen DHS bei instabilen Oberschenkelhalsfrakturen. 71. Jahrestagung Deutsche Gesellschaft für Unfallchirurgie DGU, Berlin, Germany, 2007
151. Windolf M, Dutoit C, Schwieger K: Treatment of unstable femoral neck fractures: Is a helical-shaped implant a
superior alternative to the dynamic hip screw? OTA, Boston MA, USA, 2007
152. Wuertz K, MacLean JJ, Stinnett-Donnelly J, Barbir A, Roughley P, Alini M, Iatridis JC: Biological response of the
intervertebral disc to chronic dynamic compression – An in vivo animal study. 34th Meeting of the International
Society for the Study of the Lumbar Spine, Hong Kong, China, 2007
153. Wuertz K, MacLean JJ, Stinnett-Donnelly J, Barbir A, Roughley P, Alini M, Iatridis JC: Remodeling of the intervertebral disc due to chronic dynamic compression. 53rd Annual ORS, San Diego CA, USA, 2007
154. Zhou GQ, Yee A, Chan D, Alini M, Cheung KMC: Hypoxia-related and stem cell-like phenotypes of young,
adult and aged intervertebral disc cells. 34th Meeting of the International Society for the Study of the Lumbar
Spine, Hong Kong, China, 2007
AO Research Institute
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Switzerland
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Activity Report 2007

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