Rapid Bone Regeneration through Biomimetic Solutions

Rapid Bone Regeneration
through Biomimetic Solutions
Pre-Formed Bone Substitute
Hydroxyapatite biomaterial with a trabecular structure
Moldable Bone Substitute
Magnesium substituted hydroxyapatite nano-crystals
Flexible Bone Substitute
Collagen-hydroxyapatite composite biomaterial
Engineered for Orthopaedic surgery
Flexible Bone Substitute
RegenOss represents an innovative concept in bone grafting. It is a collagenhydroxyapatite composite biomaterial designed and engineered at macro-, micro-,
and nano-scale to promote bone regeneration.
Moldable Bone Substitute
SINTlife Paste, Putty and Granules are synthetic fully resorbable grafts made of
magnesium substituted hydroxyapatite nano-crystals.
Pre-Formed Bone Substitute
ENGIpore is an innovative porous hydroxyapatite biomaterial with a trabecular
structure similar to that of natural bone.
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1
Contents
The Science behind successful Bone Regeneration
3-4
Human Bone Composition5-6
The bone healing process7-8
The Portfolio9-10
Geometrical Biomimetism11
Chemical Biomimetism12
Speed of Regeneration13-14
Portfolio in Practice / Case Studies
15-22
2
The Science behind successful Bone Regeneration
By using the most innovative nanotechnologies, Finceramica has developed a range of
biomimetic bone grafts capable of mimicking the composition, structure, morphology, and
chemico–physical properties of natural tissues.
Hydroxyapatite-based and enhanced with magnesium or with type 1 collagen, these
unique biomimetic materials are recognised and accepted by the body as “self”, thereby
not triggering any immune response.
Their nano-, micro- and macro- structure and their chemical composition play a decisive
role in the bone remodelling process, by permitting an extensive communication between
the biomaterial and the surrounding tissue matrix and cells.
The grafts promote the ingrowth of cells facilitating the bone regeneration process,
creating an ideal environment, thus activating the biological cascade, leading to new bone
formation.
3
Calcium-phosphate ceramics
Several types of calcium-phosphates are currently used in clinical practice
as bone substitutes
2.00
(Calcium / Phosphorus)
1.80
Human Bone: 1.71
1.60
1.40
1.20
1.00
0.50
0
Octacalcium
phosphate
(OCP)
Tricalcium
phosphate
(TCP)
Hydroxyapatite Human Bone
(HA)
Tetracalcium
phospate
(TCPM)
4
Human Bone Composition
Bone Structure
BONE is an organised assembly of structural units hierarchically ordered at increasing size levels.
Bone Composition
70% Inorganic matrix
- Hydroxyapatite Ca/P = 1.71
22% Organic matrix
- principally collagen and cells
8% Water
Lacunae containing osteocytes
Osteon of compact bone
Lamellae
Canaliculi
Haversian canal
Periosteum
Volkmann’s canal
5
Bone Biomimetism
A new concept in bone regeneration
Structure at nano, micro and macro levels • Inorganic and organic phases • Chemical polarity
Human Bone Structure
Macroscopic
Compact
Microscopic
Unmineralised
(Osteoid)
Cancellous
Mineralised
Woven Bone
(Immature)
Lamellar Bone
(Mature)
Human Bone Composition
Matrix
Cells
Organic
Collagen
Products
Inorganic
Mucopolysaccharides
Ca/P Ratio
Polarity
Non-Collagenous Proteins
Osteoprogenitor
Osteoblasts
Osteocytes
Osteoclasts
6
The bone healing process
Bone healing involves a complex biological cascade of events that can be summarised in a
4-phase process: haematoma, inflammation, bone callus formation and bone remodelling.
The bioceramic materials developed by Finceramica play an important role in guiding the
bone healing process, leading to effective tissue regeneration.
1
HAEMATOMA
Immediately after the fracture,
extensive bleeding occurs. Over a
period of several hours, a fracture
hematoma develops. The following
blood clot is colonized by cells
like macrophages, white cells,
fibroblasts and mastocytes.
INFLAMMATION
The clot is invaded by blood
vessels that bring oxygen
and regenerative cells such as
osteoblasts, preosteocytes and
chondroblasts. During this stage
soft callus is forming.
7
2
3
BONE SUBSTITUTE IMPLANT
The biomaterial placed in the intraoperative phase interacts and is
colonized by bone precursor cells,
acting as a scaffold to guide a
proper callus formation.
4
BONE CALLUS FORMATION
At this stage, the soft callus
remodels into hard callus.
Simultaneously, scaffold resorption
begins. Tissue calcification takes
place, leading to progressive
appearance of woven bone.
5
REMODELLING
Through the synchronized action
of osteoclasts and osteoblasts,
the bone is remodelled to reach
it’s native biofunctional shape
and mechanical resistance. The
bioceramic graft is now completely
reabsorbed or fully osteointegrated.
8
The Portfolio
The SEM images show that the RegenOss nanostructure is comparable to human bone
nanostructure: magnesium-hydroxyapatite nanoparticles are nucleated into collagen fibres
to recreate a favourable environment for new bone formation as in our body.
Micro-Structure (SEM image)
Collagen fibres
Hydroxyapatite
2µm
(Mg-HA nucleated on type I collagen fibres)
500 nm
bres
ydroxyapatite
500 nm
9
Human bone
Perfectly mimicking the human bone
mineral phase, SINTlife is composed
of magnesium-substituted
hydroxyapatite to promote bone
regeneration. The X-Ray diffraction of
SINTlife has common characteristics
when compared to that of natural bone.
The microscopic image highlights the
perfect geometrical and structural
biomimetism of ENGIpore in respect to
the human bone. The interconnected
porosity allows cells to colonise the
scaffold, thus recreating the human bone
trabecular structure.
200
Counts
150
100
50
0
24
26
28
30
32
34
36
38
2-Theta
SINTlife
Finceramica’s synthetic Hydroxyapatite
125
Counts
100
75
50
25
0
24
26283032343638
2-Theta
Natural Bone
Human bone inorganic matrix
10
Geometrical Biomimetism
Hydroxyapatite (HA)
Max
Composite Material
RegenOss is a fully biomimetic scaffold, its unique structure and chemical
composition confer characteristics replicating that of human bone.
Nanostructure
SINTlife Paste, Putty and Granules are synthetic fully resorbable grafts made
of magnesium substituted hydroxyapatite nano-crystals.
Macro Porosity
Micro Porosity
Pore Interconnection
ENGIpore is an innovative porous hydroxyapatite biomaterial with a trabecular
structure similar to that of natural bone.
Min
11
Chemical Biomimetism
Reflecting Human Biochemistry to enhance bone regeneration
Z-Potential
The Z-potential facilitates interaction between Mg-HA, water molecules, proteins and cells, including
mescenchymal stem cells, osteoblasts etc by ensuring the electro kinetic potential of the interface
between bone and implant is appropriate.
Cells
Proteins
H2O
Mg
Mg
Mg
SINTlife / Regenoss
12
Resorption Kinetics
Distal femoral fracture
Acetabular defect filling
% Mass
Spine fusion
6-9
Remodelling Half Life
13
Tarsal fracture
Posterolateral fusion
Proximal humerus fracture
Femoral cysts
Lumbar ALIF
Open wedge osteotomy
6-18
24-36
Metacarpal fracture
Months
14
Portfolio in Practice
Clinical Cases: PRE OP X-RAY
Pre-operative investigations
suggests a large acetabular defect
will be found once the acetabular
cup has been removed.
The defect was measured
and prepared.
The Regenoss was moistened
with blood to allow the material
to become flexible and easy to
insert into the defect.
The Regenoss patch was placed onto
the floor of the acetabulum and gently
formed into place. The acetabular
cup was then implanted directly on
top of the bone regeneration graft.
Immediate post-op x-ray.
Six month follow-up showing
good bony growth.
Courtesy of Mr. Tim Waters, Consultant Orthopaedic Surgeon
St Albans City Hospital, UK
15
Type of Trial
prospective, randomised, controlled
Inclusion Criteria
31 Patients undergoing osteotomy for varus deformity
Age 25-60 y/o
10 mm minimum correction
Plate stabilization
Treatments
SINTlife paste
Lyophilized human bone chips
Lyophilized
bone chips
Principle Investigators :
(Prof. Giunti)
(Prof. Giannini)
Courtesy of Prof. Giunti & Prof. Giannini, Rizzoli Orthopaedic
Inolitite, Bologna, Italy
16
Portfolio in Practice
Clinical Cases:
HIGH TIBIAL OSTEOTOMY FOR GENU VARUS
Results: 3 months post-operative radiograph
SINTlife
Lyophilized Bone
“Three months after surgery, patients who received the Lyophilized Bone
showed delayed bone remodelling, with bone chips still present. However
SINTlife® subjects showed appreciable regeneration.”
Courtesy of Dr. Dallari, Rizzoli Orthopaedic Institute
17
Results: 6 months post-operative radiograph
SINTlife
Lyophilized Bone
“Six months after surgery effective bone remodelling and osteointegration were
observed in the SINTlife patients and was significantly higher than found in the
Lyophilized bone group.”
Courtesy of Dr. Dallari, Rizzoli Orthopaedic Institute
18
Portfolio in Practice
Histologies at 45 days post-op
“…in Sintlife subjects, a discrete remodelling process was shown, even if,
conspicuous residues of the graft material were often present. Lyophilized
Bone patients demonstrated a discrete remodelling process, but, in some
cases, fibrous tissue surrounding the scarcely integrated bone chips was
present.”
Light micrographs of the tibia needle-biopsy from patients of
SINT-life® in the site of graft insertion.
Light micrographs of the tibia needle-biopsy from patients with lyophilized
bone chips in the site of graft insertion.
Lyophilized bone Patient
“Fibrous tissue around bone
chips. Original magnification
x10”
19
“At twelve months follow-up, Sintlife patients showed a higher
osteointegration percentage (41%) compared to Lyophilized Bone patients
(31.6%).”
Pecentage of graft integration
Group ✝
II
III
*p
6 weeks^
4.9 ±1.9
(2.4)
0.0-26.3
2.3 ± 0.7
(1.6)
0.0-5.2
0.31
3 months^
17.6 ± 2.9
(14.2)
5.2-36.1
13.1 ± 2.8
(9.9)
7.1-27.8
0.36
6 months^
28.7 ± 3.3
(31.8)
11.9-44.7
19.7 ± 3.3
(16.8)
10.6-34.2
0.07
12 months^
41.2 ± 4.8
(40.9)
18.4-74.9
31.6 ± 6.3
(25.2)
14.8-61.2
0.25
Courtesy of Dr. Dallari, Rizzoli Orthopaedic Institute
20
Portfolio in Practice
Used material:
Critical Size Defects
Clinical Case
Trauma
Pre-operative X-ray
Engipore cylinder
inserted
Courtesy of Dr. Landi, Policlinico Modena
21
Post-operative X-ray
Custom Bone Using
Technology
Clinical Case
Pseudoarthrosis of the ulna with 4 cm bone gap treated with
CustomBone ServiceTM and stem cells.
Pre-operative X-ray
Post-operative
X-ray
Custom bone
prothesis
implanted
Post-operative X-ray
at 14 months
Quarto R., Marcacci M. et al. “Repair of large bone defects
within the useof autologous bone marrow Stromal cells.”
N Engl J Med 2001; 334 (5) : 385-6.
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Manufacturer
FIN-CERAMICA FAENZA S.p.A.
Via Ravegnana, 186 – 48018
Faenza (RA) Italy
Distributed By:
JRI Orthopaedics is wholly owned by
Orthopaedic Research UK
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18 Churchill Way, 35A Business Park, Chapeltown, Sheffield S35 2PY
T: 0114 345 0000 F: 0114 345 0004 W: www.jri-ltd.co.uk
ORT/VS02/09/2012