3D Bioprinting of human transpant organs – A patent

3D Bioprinting
of human transpant organs
– A patent landscape
researched by Mohsan Alvi and Matthew Duckett for Coller IP
Prepared by Robert Gleave
July 2014
This White Paper combines work performed by Mohsan Alvi and Matthew
Duckett during their studies at Coller IP in 2014
.
3D Bio-­‐printing of Transplant Organs – A Patent Landscape A Market Research Project conducted in collaboration with Coller IP Mohsan Alvi Lady Margaret Hall Supervised by: Robin Cleveland Trinity Term 2014 3D Bio-­‐printing of Transplant Organs – A Patent Landscape This
report has been produced by Mr Mohsan Alvi whilst studying at Coller IP, as a formal
contribution towards his PhD studies in from the Centre for Doctoral Training in Healthcare
Innovation at the University of Oxford. The report is made available for use but the contents
this document may not be reproduced in whole or part, nor passed to any organisation or
of
person
without the specific written permission of Coller IP Management Ltd.
Please note that the views expressed here on companies and individual project cases draw
information available in the public domain. We have not sought to establish the reliability
on
of these sources. Accordingly no representation or warranty of any kind (whether express or
implied)
is given by Coller IP to any person as to the accuracy or completeness of the report.
Moreover the report is not intended to form the basis of any investment decisions and does
not absolve any third party from conducting its own due diligence in order to verify its
contents. Coller IP accepts no liability of any kind and disclaims all responsibility for the
consequences of any person acting or refraining to act in reliance on the report or for any
decisions made or not made which are based upon this report.
2 3D Bio-­‐printing of Transplant Organs – A Patent Landscape ABSTRACT 3D bio-printing is the process of creating spatially-controlled cell patterns, in which the
behaviour of biological tissues can be reproduced. This ideally extends to printing complete,
viable organs for transplant. Bio-printed organs could potentially decrease transplant organ
rejections and increase the availability of organs for critically ill patients. The ability to
produce viable organs is still thought to be 10-15 years away, but functioning micro-organs
have been produced.
The 3D bio-printing market is still in its infancy, with the majority of income coming from
grants. But this is expected to change over the next decade with the predicted emergence of
a $3 billion bio-printing market.
This report looks at the patent landscape surrounding bio-printing technologies and
companies that are active in their research and development. 3 3D Bio-­‐printing of Transplant Organs – A Patent Landscape Section 1 – Introduction
3D-printing, as described by Schubert et al., is the process of creating a three-dimensional
object, by adding successive layers of a material (usually plastics, metals and other
polymers) on top of each other [1]. This differs from machining, e.g. using lasers to cut
shapes out of a larger bulk of material, which is a subtractive method. 3D printing is
therefore also known as additive manufacturing.
Printing plastic objects, for example, can be achieved by keeping plastic at a temperature
just above its melting point. The “thermoplastic” then solidifies almost immediately once
“printed” as it cools down. This process is called fused deposition modelling.
Alternatively, it is also possible to create a three-dimensional object by the selective curing of
a resin using lasers, as is the case in stereolithography. The latter method was used by
Charles W. Hull, the man credited with the invention of the first 3D-printer. He mentions the
high cost and effort associated with creating prototype models as the motivation for his
invention.
A 3D printer consists of one, or multiple material dispensers, which can move in three
dimensions. It requires a control signal from software that can process 3D printing files.
These convert a computer design into a slice-by-slice model to be printed.
Within healthcare, 3D printed prosthetics and implants have already been in the market for
some years. These are created using 3D printing technology due to its ability to create
completely new designs with minimal design-specific setup. The associated time saving is
also why 3D printing is referred to as rapid prototyping.
3D bio-printing is a field of tissue engineering, which aims to print functional human tissue
from thin layers of cells. Bio-inks consist of a suspension of cells in a liquid medium, and
hydrogels are used to hold cells in a geometric construct once printed. Printing viable
organs, as shown in figure 1.1, is not possible as of yet, as organs are very complex. Most
printed organs are not viable for very long, and perfusion of organs after printing is still an
open issue [2].
Figure 1.1 – The prospects of printing complete, functional human hearts are still 10-­‐15 years away ©explainingthefuture.com [3]
4 3D Bio-­‐printing of Transplant Organs – A Patent Landscape The potential benefits of bio-printing organs are vast: the demand for transplant organs
significantly outweighs the number of available organs (see figure 1.2). The average time on
the transplant waiting list for a kidney transplant is five years [4]. By increasing the number of
available organs, this demand could be met. This would not only improve patient outcomes,
but also reduce the financial burden on healthcare services providing intermediate care,
such as dialysis.
Additionally, donated organs can be rejected by a patient’s body. 3D printed organs can be
based on a patient’s own cells, which can be cultured and could potentially reduce the risk of
rejection during transplantation.
Figure 1.2 – Yearly number of transplants, patients on waiting list, living and deceased donors in the United States. [5] The ability to design and print organs leads to ethical concerns, and Gartner predicts a
global debate about the regulation or banning of bioprinting for human use by 2016 [6]. One
concern is long-term effects of bio-printed organs on the human body and the safety thereof.
Another concern is the difficulty to guarantee that printed organs are of the highest quality,
and equally available for all patients – concerns that arise from commercialising life saving
transplant organs.
5 3D Bio-­‐printing of Transplant Organs – A Patent Landscape Section 2 – Market size
Since 3D bio-printing is still in its infancy, there is very little publically available market
information, although market research reports are available [7][8].
A hype curve, for example that shown in figure 2.1 for 3D printing applications, shows how
high current expectations are of a technology and how close we are to achieving them.
Points higher up on the curve in the y-axis have higher expectations, and points on the curve
further to the right on the x-axis are closer to being realised. We can see that prototyping,
the original thought behind 3D printing, is closest to the “plateau of productivity”, which
denotes the time-point where the technology can be used productively. Medical research,
including 3D bio-printing, however is still in the early “technology trigger” phase. With more
mainstream media outlets covering the exciting prospects of bio-printing, expectations of the
public, and also investors are raised. With the realisation, that we are still decades away
from bio-printed transplant organs, investors may become more reluctant to invest.
Figure 2.1 – Hype curve showing technology expectations against how close they are to be achieved [7]. So far, bio-printing companies are not generating substantial revenues, and most of their
income is derived from grants. Estimates in 2013 placed the entire 3D printing market at
$700 million, with only 2% of that being invested 3D bio-printing [9]. This value was a 109%
improvement from 2012, and expected to rise another 79% in 2014 to hit US$1.3 billion.
According to one report, the 3D printing market is expected to grow to $7 billion by 2025, of
which at least $3 billion will be attributed to bio-printing [7]. This may be a conservative
estimate, with Canalys estimating a market size of $5.4 billion by the end of 2018. 3D bioprinting is an exciting field with a huge potential market and potential cost benefit to the
healthcare sector, especially when costs of long-term care for patients on transplant waiting
lists are factored (over £30,000 per annum for dialysis in the UK)[10].
6 3D Bio-­‐printing of Transplant Organs – A Patent Landscape Section 3 - Notable Companies
There are a number of companies that sell bio-printers for laboratory experiments. This
section looks at some notable companies that either produce 3D bio-printing equipment, or
bio-printed materials.
Organovo Organovo claims to “design and create functional human tissues” using their “proprietary
three-dimensional bioprinting technology” [11]. They aim to provide pharmaceutical
companies with Organovo's NovoGen MMX Bioprinter, which was selected as one of the
"Best Inventions of 2010" by TIME Magazine. They also claim to have designed a computer
model of a human liver, and have printed liver prototypes.
Organovo stands out from other 3D bio-printing companies, in that it is trading on the stock
market, as “Organovo Holdings, Inc. (ONVO)”. Despite having negligible turnover, Organovo
attracted significant investment and has a current market capitalization of over $550 million.
According to Mikael Renard, commercial executive vice president at Organovo, we are still
decades away from 3D printed organs, though more funding could shorten that time-scale.
EnvisionTEC German private company EnvisionTEC claims to be a leading global provider of 3D printing
solutions. They specialise in a wide variety of 3D printing applications, such as medical
devices, dentistry, jewelry and toys. Additionally, EnvisionTEC has a biofabrication line of
products, with the BioPlotter® standing out. The BioPlotter® is a 3D bio-printer (Figure 3.1),
which has been available since 2001, and is available for under $200,000 [12]. The printer is
capable of printing a wide variety of organic and inorganic materials and includes controlling
software.
Figure 3.1 – EnvisionTEC BioPlotter® ©EnvisionTEC [13] GeSim German private company GeSim is a spin-off from the Rossendorf Research Center and
specialise in sub-microliter liquid handling. Their BioScaffolder 2.1 is a 3D bioprinter, capable
of creating bio-scaffolds for tissue engineering purposes. According to an article in
7 3D Bio-­‐printing of Transplant Organs – A Patent Landscape 3DPrintingIndustry.com, the Dutch government has invested $1 million in the Utrecht Life
Sciences Biofabrication Facility to produce living tissue using GeSim’s BioScaffolder.
Figure 3.2 – GeSim BioScaffolder 2.1 ©GeSim [14] OxSyBio University of Oxford spin-out OxSyBio aims to produce tissue-like synthetic materials for
wound healing and drug delivery, with a long-term goal of producing synthetic tissues for
organ repair or replacement. They recently raised £1 million with IP Group plc to develop
their 3D droplet printing technology.
regenHu regenHu is a Swiss company that creates biomanufacturing solutions. The company offers a
range of 3D bio-printers, bio-inks and 3D tissue modelling software. The BioFactory® stands
out as a 3D bio-printer and incubator that creates a cell friendly environment and claims to
allow the production of organotypic tissues.
Figure 3.3 – regenHU BioFactory® ©regenHu [15] Section 4 - Patent searches
To investigate the patent landscape of 3D bio-printing, a series of patent searches were
undertaken using Thomson Reuters’ “Thomson Innovation” software. The scope of
searching was restricted using the following criteria:
8 3D Bio-­‐printing of Transplant Organs – A Patent Landscape 1. Patents with filing dates after 01/01/1994.
The World Trade Organization (WTO) specifies in the Agreement on Trade-Related
Aspects of Intellectual Property Rights (TRIPS Agreement), that a patent term is
twenty years after its filing date[16].
2. 3D bio-printing of mammalian tissue for use in humans
The patents should describe methods for using human or animal cells to print organlike structures for use in humans.
Search terms were selected in the following ways:
•
Literature review on the subject of organ printing for an overview of commonly used
terms in the field.
•
Patents from known companies/applicants were scanned for recurring keywords in
the title, abstract and claims.
•
Cooperative patent classification (CPC) codes (Table 4.1) were noted for applicable
patents.
The choice of search terms was an iterative process of trying to improve the percentage of
patents returned, that were applicable to the project scope – the “hit-rate”. One significant
difficulty in improving the hit-rate, was the large number of mostly irrelevant patents making
a small reference to a potential use of their patent for bio-printing. This was often the case
with terms defining a field of application, e.g. “medical”. Some keywords could be applied to
different fields, e.g. “cells” returning patents about fuel cells. Searches were therefore
narrowed down by setting rules for relevant adjacent terms, or combining keyword searches
with applicable CPC codes. A summary of applicable search terms is given in table 4.2.
Since 3D bio-printing is still a new field of research, many terms are being coined by
inventors and companies alike. Therefore, as more research is conducted, different search
terms may need to be added to find all applicable patents.
Another consideration to be made is that developing more robust bio-inks is a significant
factor for bio-printing to be successful. Patents describing such are difficult to find, due to 1)
the high number of tissue engineering patents, 2) the lack of explicit mention of 3D printing
applications.
9 3D Bio-­‐printing of Transplant Organs – A Patent Landscape Cooperative patent
classification codes
Description
B28B 1/001
Rapid prototyping, additive manufacturing
B29C 67/0051
Rapid prototyping, additive manufacturing
C12M 21/08
Cells cultivation for tissue engineering
C12N 5/00*
Cultivation of human/animal cells
Table 4.1 – Cooperative patent classification codes. An asterix (*) denotes matching codes
up to the asterix are also applicable
Topic
Search terms
3D printing
Additive manufacturing, additive printing, rapid prototyping, 3D printing,
three-dimensional printing, inkjet printing
Bio-printing
bio-printing, bio-plotting, bio-fabrication, tissue patterning, organ printing,
computer-aided tissue engineering,
Bio-materials
Bio-material, bio-ink, bio-paper, human/animal/mammalian cell,
human/animal/mammalian tissue, scaffolding, hydrogel, gelatin,
matrigel,
Table 4.2 – Terms used for patent searches (truncation and search operators not shown).
Note that some terms need to be used in combination with codes or other search terms to
return applicable patents.
10 3D Bio-­‐printing of Transplant Organs – A Patent Landscape 11 Figure 5.1 – Biomedical applications of 3D printing patent landscape.
Section 5 – Patent Landscape
3D Bio-­‐printing of Transplant Organs – A Patent Landscape Figure 5.2 – 3D bio-printing patent landscape consisting of patents specifically about methods for printing human cells
cetissue.
12 3D Bio-­‐printing of Transplant Organs – A Patent Landscape Patent landscaping is a useful tool for the visualization of patent density with respect to
different topics. The patent landscapes in figures 5.1 and 5.2 were created using Thomson
Innovation Themescape. Patents are clustered together into similar groups. These were then
labelled by inspection.
Figure 5.1 shows a patent landscape generated from a patent document set identified using
the search terms in tables 4.1 and 4.2, which amounts to a more general overview of 3D
printing in biomedical applications. A large proportion of the patents in this landscape focus
on the 3D printing of biosensors, small medical appliances and implants. There are also a
range of patents that describe image analysis techniques that can produce printable models,
and a significant number of patents describing ink handling. Among bio-printing patents, the
majority of patents describe bone printing, or cellular implants that can aid bone healing.
Many of these patents describe techniques that may also prove useful for organ printing, but
do not specify such as their primary function.
Figure 5.2 shows a patent landscape which has been generated from a more focused
document set (detailed search terms are given in the appendix). The document set was
identified using more specific searches which were conducted separately and then
combined, and some patents were manually removed if not applicable. This patent
landscape, which focuses specifically on the topic of bio-/organ printing, and will be
discussed further in the following sections of this report, and consists of just under 200
patent families.
3D Bio-­‐printing Landscape Bio-printing patents can be broadly classified into three groups: 1) the process of printing, 2)
bio-inks and 3) scaffolds. These can be seen in figure 5.2, where bone and scaffolding
methods are an area that contains a relatively high number of patents. In comparison, there
is less work on hydrogels, and extracellular matrix design, which are vital for creating softtissue organs. Bio-inks, cartridges and dispensing methods are also an area with significant
proportion of patents.
Figure 5.3 – Top 10 CPC codes of patent families in figure 5.2 13 3D Bio-­‐printing of Transplant Organs – A Patent Landscape The top 10 CPC codes which have been assigned to the ~200 patent families identified
relating to bio-printing are shown in figure 5.3. These include codes for additive printing
(B29C 67/0055, B29C 67/0081), medical equipment (B29L 2031/753), materials for printing
(C12N 5/0068, C12N 2533/40), and description of products (A61L 27/18, A61L 27/38, A61F
2/28). Some codes, as in the case of codes starting with B29C, C12N and A61L, were used
as search terms and are, therefore, more prevalent. This could potentially skew the results in
their favour. However, since the codes were chosen as a result of reading a range of 3D bioprinting patents, and were used to reduce the number of inapplicable patents appearing in
our searches, they are representative of a 3D bio-printing patent population.
A code specifically for bio-printing does not exist.
Figure 5.4 – Top applicants of patent families in figure 5.2
The top applicants in the 3D bio-printing landscape of figure 5.2 are shown in figure 5.4.
Organovo and Therics lead the statistic for commercial companies, whilst Drexel University
and Massachusetts Institute of Technology represent universities, with five patent families
each. Other notable applicants include the Universities of Wake Forest, Virginia, Texas and
Missouri and the US Navy, with four patent families each.
Amongst inventors, the most patents have been filed by Wei Sun, with nine patent families to
his name. The top ten inventors have each filed at least four patents.
The number of patent families filed each year has risen from three patent families in 1996 to
over 30 patent families in 2013, as shown in figure 5.6 (n.b. due to the delay between filing
and publication of a patent application, the number of patents filed in 2012 / 2013 is
expected to be higher than shown on the figure). This trend is representative of a new area
of science and shows how the 3D bio-printing IP landscape is still in its infancy. The
growingrend in developments and inventions is likely to have resulted from the exploitation
of a number of breakthroughs in the field and increased funding for research resulting in
more research facilities.
14 3D Bio-­‐printing of Transplant Organs – A Patent Landscape Figure 5.5 – Top 10 inventors of patent families in figure 5.2
Figure 5.6 –Number of patent families filed 1996-2013 (date of filing of earliest patent family
member shown). N.B. data for 2012 / 2013 incomplete
15 3D Bio-­‐printing of Transplant Organs – A Patent Landscape Section 6 – Organ Printing Technologies
There are multiple aspects to the 3d bio-printing of tissues and organs:
1. Pre-processing: Computer-aided design of organ structure to be printed
2. Tissue engineering: The method of creating tissues and organs from biomaterials,
where the focus lies on how to design the tissue
3. Printing: The method of creating tissues and organs from biomaterials, where the
focus lies on how to deposit cells to form a construct.
In terms of printing, a few key patents describing methods for depositing cells in a geometric
structure are described below.
One of the first patents describing the 3D printing of biomaterials was filed by William
Murphy in 2000. It claims to be an advantageous method for patterning and/or mineralizing
biomaterial surfaces [17]. The patent describes the usage of lithography techniques for
patterning polymers for bone regeneration implants. The printing technique is that of
lithography, in which the selective curing of a light-sensitive material results can be used for
3D printing.
EnvisionTEC filed a patent detailing a versatile 3D printer that can be used to print a variety
of materials at a range of operating temperatures in 2000 [18]. The printer uses dispensers,
which can move in three-dimensions, to discharge fluids to form a solid structure (see figure
6.1). The fluid is metered into microdots to produce microstrands, which in layers produce
the desired structure. The ability to regulate the operating temperature improves the viability
and bioactivity of cells during the printing process.
Organovo also filed a patent in 2013, detailing its design for a bio-printer using a UV light, to
optionally expose cells to light [27].
Figure 6.1 – EnvisionTEC 3D printer design [17]
In terms of pre-processing and software, two interesting patents are mentioned below.
16 3D Bio-­‐printing of Transplant Organs – A Patent Landscape Hollister et al. of the University of Michigan filed a patent detailing computer software that
takes into account the property of biomaterials for the design of microstructures [19]. This is
an important aspect of 3D bio-printing, as the design is equally important as the printing
process.
Sandia Corp filed a patent in 2004, describing a method for creating three-dimensional,
biocompatible scaffold structure [20]. This is achieved first designing the three-dimensional
structure on a computer and passing this file to a 3D printer that can interpret it.
Bio-printing technologies for tissue engineering can be broadly categorized into the following
1. Cell-free scaffolds
2. Cellularized scaffolds
3. Tissue-printing without scaffolds
Cell-free scaffolds are designed to recruit stem cells, and provide mechanical support for the
growth of new organs and tissues. They then degrade over time and are replaced as the
cells regenerate their extracellular matrix.
An early patent in this field was filed by the National University of Singapore in 2001 [21].
The method describes an additive manufacturing method, fused deposition, to create a
scaffold based on a CAD model. The model is converted into mathematically calculated
horizontal slices for printing. These scaffolds can then be seeded with biomaterials to
stimulate tissue growth.
Cellularized scaffold consist of scaffolds with cells seeded onto them. These usually make
use of hydrogels to create spatially heterogeneous structures.
A patent filed by the Cornell Research Foundation in 2005 describes a method for depositing
materials onto different articles, which can be applied to creating cellularized scaffolds [22].
The invention describes a method that takes 3D tomography scans, with an automated
implant architecture design, to create viable cell hydrogel implants.
Similarly, patents from Wake Forest University describe inkjet printing methods for forming
arrays of different cell types. The patent shows that products retain their structural integrity in
vivo after implantation [23] [24].
Printing tissues directly, i.e. tissue-printing, derives from the belief that cells are biomaterials
and can form organs and tissues without the need of support structures: “…tissue
engineering can be achieved by the self-assembly of tissue components without the need for
conventional solid materials” [25].
Picoliter filed a patent for the use of focused acoustic energy to direct cells suspended in a
carrier fluid [26]. This allows the precise printing of individual cells on a substrate, potentially
allowing complete freedom in tissue design.
17 3D Bio-­‐printing of Transplant Organs – A Patent Landscape Conclusions / Recommendations
Organ printing is still in its infancy, and it is estimated that another 10-15 years of research is
necessary before complete, viable transplant organs can be printed. The market is expected
to grow rapidly over the next decade, with bio-printing amounting for a significant proportion
of overall 3D printing sales. The total bio-printing market size is expected to pass $3billion in
the next decade. There are less than 200 patent families found on an IP landscape of the
area that detail the process of bio-printing and technologies directly related to the production
of 3D printed organs and tissue. Some key differences in technologies come from different
scaffolding approaches for cells and deposition methods. These patents can be classified
into 1) pre-processing, i.e. computer modelling, 2) printing, where the tissue engineering
aspect is of concern, and 3) printing, where the method of placing cells is of concern. There
are three sub-areas of 3D bio-printing, from a tissue engineering perspective, which include
1) cell-free scaffolds, 2) cellularized scaffolds, 3) tissue-printing without scaffolds.
Cell viability and perfusion after printing is a concern, and printer heads are being modified
to print at even higher resolutions. As such, intellectual property in this field is very valuable,
and any advances in improving the resolution of printing, i.e. the ability to print smaller
structures, will be very valuable for the advancement of the field.
18 3D Bio-­‐printing of Transplant Organs – A Patent Landscape References
[1] C. Schubert, M. C. Van Langeveld, and L. A. Donoso, “Innovations in 3D printing : a 3D
overview from optics to organs,” pp. 159–161, 2014
[2] R. P. Visconti, V. Kasyanov, C. Gentile, J. Zhang, R. R. Markwald, and V. Mironov,
“Towards organ printing  : engineering an intra-organ branched vascular tree,” pp. 409–420,
2010.
[3] Explaining the Future. Available at http://www.explainingthefuture.com/bioprinting.html
[4] Gift of Life Donor Program Statistics, 2014.
[5] United Network for Organ Sharing (UNOS), Transplant statistics 1994-2006
[6] Stamford, Conn., Gartner Press Release, January 29, 2014
[7] IDTechX, 3D Bioprinting 2014-2024: Applications, Markets and Players, March 2014
[8] Roots Analysis Private Ltd., 3D Bioprinting Market 2014-2030, March 2014
[9] Wohlers Associates. What is 3D printing? Wohler’s Report, 2013
[10] Organ Donation NHS, Cost-effectiveness of transplantation Fact Sheet, 2009.
[11] Organovo – About Us.
Available at http://www.organovo.com/company/about-organovo
[12] Tech Guru Daily, 3D Printer Wants to Print Human Organs, July 10, 2010
Available at http://www.tgdaily.com/general-sciences-features/50596-3d-printer-wants-toprint-human-organs#4O61OY0YX6uUGCBK.99
[13] EnvisionTEC BioPlotter®, Available at http://envisiontec.com/products/3d-bioplotter/
[14] GeSim BioScaffolder 2.1, Available at http://www.gesim.de/en/bioscaffolder/
[15] regenHu BioFactory®, Available at http://www.regenhu.com/products/3d-bioprinting.html
[16] World Trade Organization. Trade-Related Aspects of Intellectual Property Rights; Article
33. Available at http://www.wto.org/english/docs_e/legal_e/27-trips_04c_e.htm
[17] Murphy WL, Peters MC, Mooney DJ, Kohn DH. inventor Mineralization and biological
modification of biomaterial surfaces. US6767928, 2000
[18] Mulhaupt R, Landers R, Hendrik J. Device and method for the production of three
dimensional objects. US6942830, 2005.
19 3D Bio-­‐printing of Transplant Organs – A Patent Landscape [19] Lin CY, Hollister SJ, Lin C-Y. Integrated global layout and local microstructure topology
optimization approach for spinal cage design and fabrication. WO2004/093657A2, 2004.
[20] Cesarano JI, Stuecker JN, Dellinger JG, Jamison RD. Method for making a biocompatible scaffold. US6993406, 2006.
[21] Toeh SH, Hutmacher DW, Tan KC, Tam KF, Zein I. Methods for fabricating a filament
for use in tissue engineering. US6730252, 2004.
[22] Lipson H, Bonassar L, Cohen DL, Malone E. Modular fabrication systems and methods.
US7625198, 2009
[23] Yoo J, Tao Xu, Atala A. Ink-jet printing of tissues. US20090208466, 2009.
[24] Xu T, Yoo JJ, Atala A, Dice D. Inkjet printing of tissues and cells. US20090208577,
2009
[25] Willams DF. On the nature of biomaterials. Biomaterials 2009; 30(30): 8.
[26] Mutz MW, Ellson RN. Focused acoustic energy for ejecting cells from a fluid.
US20020064808, 2002.
[27] Murphy K, Dorfman S, Law RJ, Le Vivian A. Devices, systems, and methods for the
fabrication of tissue utilizing UV cross-linking. US13794368A, 2013
20 3D Bio-­‐printing of Transplant Organs – A Patent Landscape 21 Appendix – Search Terms
Search Title/Abstract/Claims ID1
ID2
bio-ink or bioink or biological adj ink
((((3 or three) adj (dim* or D)) adj print*) or (bio*
adj print*)) and (organ or organs or tissue* or
human adj cell*)
((((3 or three) adj (dim* or D)) adj print*) or (bio*
adj print*)) and (bio* or organ or organs or tissue*
or human adj cell*)
((((3 or three) adj (dim* or D)) adj print*) or (bio*
adj print*)) and (bio* or organ or organs or tissue*
or human adj cell*)
((3 or three) adj (dim* or D)) and (organ or
organs) and print*
ID3
ID4
ID5
ID6
ID7
ID8
ID9
ID10
ID11
ID12
ID13
ID14
(bio-ink or bioink) or ( ((((3 or three) adj (dim* or
D)) or add*) adj print*) and (organ or organs or
tissue* adj engineer* or human adj cell* or living
adj cell* or living adj tissue*) )
(inkjet and tissue and (organ or organs)) or (inkjet
and tissue and ((mammal* adj cell*) or (stem* adj
cell*)))
(organ or organs) and print*
(organ or organs) and ((3 or three) adj (dim* or
D)) adj print*
(organ or organs or (human adj tissue) or (human
adj cell) or (liv* adj tissue) or (tissue adj
engineer*)) and ((3 or three) adj (dim* or D)) adj
print*
deposi* adj (cells or cell adj aggregat* or
biomaterial*)
(((((three or 3) adj (dim* or D)) adj print*) or
(additive adj prnt*) or (rapid adj prototyping) ) and
(organ or organs or (tissue adj engineering) or
(functional adj tissue))) or ( ((three or 3) adj (dim*
or D)) adj (organ or organs or (tissue adj
engineering) or (functional adj tissue)) adj print*)
(bio-ink or bioink) or ( (((((3 or three) adj (dim* or
D)) or add*) adj print*) or (additive adj (manufact*
or print*)) or (rapid adj prototyp*) or
stereolithograph*) or fused adj deposition) and
(organ or organs or (tissue* adj engineer*) or
((human or mammal* or stem or living) adj cell*)
or living adj tissue*) )
CPC B28B 1* or B29C 67*
C12M 21* or C12N 5*
B28B 1* or B29C 67* or
C12M 21* or C12N 5*
C12M 21* or C12N 5*
(B28B 1* or B29C 67*)
and (C12M 21* or
C12N 5*)
C12M* or C12N* or
B28B* or B29C* or
A61* or C07K*
B28B* or B29C*
B28B* or B29C*
3D Bio-printing of
Transplant Organs – A patent
landscape: further
exploration
A Market Research Project
Conducted in collaboration with Coller IP Management
A continuation of work submitted by Mohsan Alvi
Matthew Duckett
Fugro House
Supervised by: Robert Gleave
1
This report has been put together by Mr Matthew Duckett whilst attending work experience at Coller
IP management. This report is made available for use but the contents of this document may not be
reproduced in whole or part, nor passed to an organisation or person without the specific written
permission of Coller IP Management Ltd.
Please note that the views expressed here on companies and individual project cases draw on
information available in the public domain. We have not sought to establish the reliability of these
sources. Accordingly no representation or warranty of any kind (whether express or implied) is given
by Coller IP management to any person as to the accuracy or completeness of the report. Moreover
the report is not intended to form any basis of investment decisions and does not absolve any third
part from conducting its own due diligence in order to verify its contents. Coller IP accepts no liability
of any kind and disclaims all responsibility for the consequences of any person acting or refraining to
act in reliance on the report or for any decisions made or not made which are based upon this report.
2
Abstract
The aim of this report is to take a deeper look into the patents and research surrounding the
processes of the additive manufacturing of human and animal organs and tissues. Many
universities are currently involved in research regarding these processes. In addition
companies working in additive manufacturing are developing advanced bioprinters, for
example GeSim’s BioScaffolder 2.1 [1] and Organovo’s Novogen MMX Bioprinter [2].
Following on from a previous research project carried out by Mohsan Alvi, several additional
search steps were undertaken eventually leading to the discovery of some patents very
strongly linked to the development of bioprinters. Also identified were a wide variety of
research projects in progress and a number of recent discoveries made by these projects.
3
Introduction
The aim of this report is to further investigate in depth the patent landscape surrounding
the processes of additive manufacturing of human and animal organs following an earlier
landscaping study. This investigation of the patent landscape was carried out using the
following approaches:
(1) Identification of potential inventors and patent applicants in the field of bioprinting
of organs
(2) Reviewing the patent portfolios of key companies
(3) Keyword searching and landscaping analysis
The patent documents from steps (1)-(3) were then reviewed for relevance to the
bioprinting of organs and a set of key patent families identified. A citation analysis was then
carried out (step 4) with the aim of identifying any additional patents of interest.
Section 1 – Initial Search
Methodology:
An initial internet based search was carried out to identify potential inventors and
applicants of patents relating to the organ bio-printing. To obtain the following results, Mr
Alvi’s research was reviewed and companies which had already been identified that are
currently working in the field of bioprinters were listed. In order to obtain new information
within the field of 3D bio-printing of transplant organs, results relating to the previously
identified companies were excluded from the new searches. This meant that the searching
identified a new comprehensive list of companies and universities involved in the field.
All of the internet searches were made in Google™ and to begin with obvious terms, for
example “3D organ printing” and “additive manufacturing of organs and tissues” amongst
other terms identified by Mr Alvi’s report, were used as keywords in the process, however
as the search progressed more specific terms mentioned within reports e.g.
“Vascularization” or “Biofabrication” were found, enabling less publicised articles on 3D
bioprinting to be found which perhaps would not have otherwise been identified.
Results:
Internet searching identified nine universities or companies involved within the field. The
universities or companies are listed below together with any identified patent documents:
Anthony Atala, Wake Forest Institute
This search result was obtained by searching for “3D printing of organs” and is briefly
mentioned in Mr Alvi’s report in ‘Section 6 – Organ Printing Technologies’. The article
4
discovered describes “a 3D printer that uses living cells to output a transplantable kidney”
[3]. This research is being carried out by the Wake Forest Institute and Harvard University.
Patents relating to this research were found within the Thomson Innovation database by
searching for patents where the inventor is “Atala, Anthony”. Three patent families of
interest were identified: US20120089238A1, Integrated organ and tissue printing methods,
system and apparatus; US2009208466A1, Ink-jet printing of tissues; and US8691274B2,
Inkjet printing of tissues and cells. These patent families are all very relevant and are very
much linked with 3D bio-printing of organs.
Regenovo™ (Hangzhou Dianzi University)
This Chinese-based company features in an article which describes how their machine
“Prints a liver and an ear” [4] and their 3D bioprinter is also mentioned on the company’s
website [5] which describes that the printer has been jointly developed with Hangzhou
Dianzi University. The company offers research on this machine and currently claims to be
able to print tissue scaffolds for research, drug discovery and “personalized healthcare”.
No patent documents were identified with Regenovo as an assignee / applicant, however
there are a large number of patent families associated with Hangzhou Dianzi University. For
example, searching on Thomson innovation identified a Chinese patent with no
corresponding international application. This patent relates to three dimensional cell chips
based on bioprinting.
Heriot-Watt University
This University appears to be developing the printing of clusters of stem cells for the growth
of organs [6]. The University is also seen to be working with Roslin Cellab a commercial
company working predominantly in the field of stem cell research and owned by the Roslin
Foundation [7]. The scientist currently leading this research is Dr Will Shu of Heriot-Watt
University who has a background in biological chemistry, biophysics and bioengineering [8].
In terms of patent families, Herriot-Watt has applied for a number of patents although none
were identified as relating to bioprinting. Interestingly the Roslin Foundation has published
patents relating to methods for differentiation of stem cells [9].
Sydney, Harvard, Stanford and M.I.T. collaboration
Journalist Brian Krassenstein claims that scientists from these universities have “figured out
a technique, making such vascularisation possible within the 3D bioprinting process” [10].
This is supported by an article on the Sydney University website [11]. A scientist involved in
this research is Dr Luiz Bertassoni from the University of Sydney whose research
interests are centred in tissue engineering, biomaterials and biomechanics [12]. Searching
for Luiz Bertassoni as an inventor yielded no relevant patent documents.
5
Princeton University
Research led by Michael McAlpine, an assistant professor at Princeton and specialising in
Biointerfaced Nanodevices and similar topics assisted by Naveen Verma, an electrical
engineering assistant professor, and Fiorenzo Omenetto, a biomedical engineering
professor at Tufts University, is claiming, with photographic evidence, that they have
developed a 3D printed ear made up of a coil antenna and cartilage [13].
No patent families regarding this kind of 3D printing organs or tissues were found with
Michael McAlpine as an inventor at Princeton University.
Cornell University
Cornell University is currently investing in research is led by Dr Lawrence Bonassar who has
a background in Tissue Engineering [14]. Bonassar has been published showing an artificial
ear that has been 3D printed and will eventually grow into a full size ear with cartilage [15].
Lawrence Bonassar is the listed inventor of a patent family relating to the printing of living
three dimensional structures (for example US20140117586A1 and US863938B2).
University of Louisville
Dr Stuart Williams is allegedly developing a six-axis printer which is a new concept no other
company appears to be pursuing. Louisville University are said to be using this technology
to create parts of the heart to be “Assembled together with a giant, intricate 3D printer”
[16] showing that organ printing will start by printing various muscles, valves, capillaries etc.
and then using more advanced technology to assemble these components of the organ.
Stuart Williams is the named inventor of four patent families linked to cellular transplants
and tissue engineering, with one family relating to “vascularization” [17]. None of the
identified patent families have any mention of a six-axis printing.
University of Pennsylvania
“Bioengineers from the University of Pennsylvania…[are] using a 3D printer called a RepRap
to make templates of blood vessel networks out of sugar. Once the networks are encased in
a block of cells, the sugar can be dissolved, leaving a functional vascular network behind.”
[18]. This is a new way of using 3D printing instead of the standard additive manufacture of
cells.
The search “RepRap” in Thomson Innovation brings up several patent families regarding 3D
printing and one from the University of Pennyslyvania which relates to 3D printing and cells
[19].
6
Virginia Tech Intellectual Properties Inc.
A patent from Virginia Tech [20] relating to three-dimensional bioprinting was found by
searching the keyword “biofabrication” in Thomson Innovation. It has been difficult to find
any news article or scientific journal to shed any more light on this research other than what
the patent tells us. Nevertheless one of the inventors, Dr Paul Gatenholm has an extensive
background in Biomaterials and Tissue Engineering [21].
Section 2 – Reviewing notable companies
Methodology
In Mr Mohsan Alvi’s report he reviews five separate companies currently working in the field
of bioprinters: Organovo™, EnvisionTEC™, GeSim™, OxSyBio™ and regenHu™. Each of these
companies was investigated to see whether they belong to a larger company or if any
patents were registered to an assignee under a different name. We then looked at what
patent families were held under those assignee names.
All searches were made in Thomson Innovation under ‘Assignee/Applicant’ or ‘Inventor’ and
then any sub-searches for keywords were carried out in all text fields.
Organovo™
The company Organovo has applied for patents as Organovo Inc. and has seven patent
families published directly linked to that name, three of which are directly linked to
bioprinters [22]. It seems very likely that these patents coincide with the Novogen MMX
Bioprinter, which is Organovo’s current 3D Bioprinter.
EnvisionTEC™
EnvisionTEC is a large 3D printing company with more patent families than any of the other
companies investigated. Therefore the search results were refined using keywords. Two
patent families were identified which appeared relevant to the topic of tissue engineering
[23]. EnvisionTEC produce a bioprinter, the 3-D BioPlotter®.
GeSim™
Searching for GeSim using Thomson Innovation brought up a number of patent families,
however these were considered of low relevance to the current study. After further
investigation it became apparent GeSim was a spinoff from the Rossendorf Research Centre.
Unfortunately searching for patent documents from Rossendorf did not reveal documents
considered to be of high relevance to the GeSim product the BioScaffolder 2.1.
OxSyBio
7
OxSyBio does not appear to own a bioprinter product at this stage or have published
patents assigned to this company. OxSyBio are run by and also funded by Isis Innovation
who state that the technology is based on 3D droplet printing devised by Professor Hagan
Bayley at Oxford University. A search for patent documents from Isis Innovation under the
sub search of “print*” “three or 3” “dimensional” and “tissue” identified seventeen patent
families. One of these patent families contained the PCT application WO2014087175A2
‘Droplet assembly by 3D printing’ which appears to be highly relevant to OxSyBio’s
technology.
RegenHu
RegenHu appear to offer the product BioFactory® however searching using Thomson
Innovation identified only two published patent families under that name. Neither relate to
3D bioprinting. It transpired that RegenHu belong to the CPA Group SA who do not appear
to have any patents involving bioprinting.
Regenovo™
This company was not identified by Mr. Alvi however it as a company which produced a
BioPrinter. See Section 1 – Initial Search, Hangzhou Dianzi University and Regenovo™ for
more information.
Section 3 – Keyword Searches
Methodology
Within Mr Alvi’s report he carried out several keyword searches. In this study some of the
same keywords were used together with a number of new search terms (see Appendix 1)..
Firstly we searched the keywords in the Titles/Abstracts/claims giving us seventy six quite
relevant results (Search A) and then searching in all text fields created a list of 3591 results.
Some were relevant to our research however, the majority related to other matters (Search
B).
Results
Within Search A’s results, after a brief analysis of the contents of each patent, we identified
seven particularly relevant patent families involving 3D bioprinters and tissue scaffolding
(shown in Appendix 1). Inventors and assignees varied between notable companies, for
example, Organovo and Anthrogenesis Corp. and some universities for example, Cornell and
New York.
8
Search B was too large to analyse all of the patent families within this project, therefore a
Patent Landscape of all of the results was created using Themescape™ and then specific
keywords were searched within the landscape. See Figures 1-4.
Keywords
Red – Bioprinter
Green – Inkjet and
listed products
Figure 1 - Printer Products
9
Assignee / Applicant
Yellow – Organovo
Green – EnvisionTEC
Red – GeSim
White – Overlaps
Figure 2 - Notable Company Comparison (overlap = more than one named applicant)
Keywords
Red – Organs
Yellow- Tissues
Green – Cells
White – Overlaps
Figure 3 – Organs (overlaps – document included more than one named keyword)
10
Keywords
Red – Heart
Yellow – Lungs
Blue – Skin
Navy – Pancreas
Pink – Kidney
Green – Liver
White – Overlaps
Figure 4 – Body Targets (overlaps – document included more than one named keyword)
Analysis
Figure 1 shows more references to bioprinters and words surrounding it, compared to Inkjet
and products such as the Novogen MMX BioPrinter, with little overlap of terms. This
suggests that the market in which standard 3D printing operates is very different to that of
3D bioprinting because Inkjet is a commonly referenced to describe the standard 3D printer
developments. As there is no overlap between the keywords, no modified inkjet printers
appear to be being described within the patent landscape.
Figure 2 raises an interesting point that the referenced companies appear to be undertaking
collaborative work because at least three of the results are shown as overlaps. On a large
scale the investigated companies have minimal published patents, most likely because they
will have highly specialised and complex products.
In regards to Figure 3 it is interesting to see that the highest proportion of patents are
within heart and skin treatments and research. “Skin” in particular rarely overlaps with the
other organ work.
Figure 4 shows hundreds of crossovers and results and so is more difficult to analyse
however it appears that organs, particularly when mentioned on their own are less common
than tissues or cells references.
11
Section 4 – Citation Analysis
Methodology
In order to identify more patents related to 3D bioprinting of organs, we looked at the
citations of a select group of the patents we had already found. We selected fifteen patents
[24] from a list of twenty five identified from previous searches, as these patents, when
assessed in more detail were considered to be highly relevant to the research.
From these fifteen patents, we extracted family members and looked at all of the citations
from those patents from one generation forward and one backwards. From this list we then
reviewed the 129 results with close analysis to identify any more relevant patents to our
research.
After this we then looked at a list of the citations from the patent families of the original
fifteen and identifying, by eye, the patents with the largest number of citations because
these had the potential to be key inventions within 3D bioprinting. We then used these to
create citations maps of Assignees/applicants to obtain a visual representation of who was
involved in patents regarding 3D bioprinting.
Results
Within the analysis of the citation found we identified nine patents that we had already
identified in our searches and five new patents [25] of high relevance. These five new results
were all from new universities that we had not yet identified as universities involved in 3D
Bioprinting, furthering our research in this field.
From a list of seventy patents we chose three patents with large numbers of citations for
analysis. See Figures 5-7
12
Figure 6 - EnvisionTEC US6942830B2
Figure 5 - Wake Forest University of Health US8691274B2 Backwards Citations
13
Figure 7 - Wake Forest Institute US20090208577A1
Analysis
Figure 5 shows points of interest, firstly DE410314A1, a patent published by Jobs S.p.A.
involving a “three dimensional plotter” and EP426363A2 another “three dimensional
creating apparatus” published by Stratsys Inc.: both backwards citations from EnvisionTEC’s
patents suggesting that EnvisionTEC is building upon past technologies regarding 3D
printing. Secondly, looking at the forward citations, EnvisionTEC have eight patents in which
US6942830B2 has been included in the citations so it appears that EnvisionTEC is also
building on its own past patents and products
Regarding Figure 6 and 7 both has a large number of documents that have been cited during
their examination process suggesting that these patents incorporate a significant number of
other patents, ideas and process. Most of these patents are related to either: 3D printing
and additive manufacturing; or Bioprinting and tissue scaffolds, a few examples of this
would be WO20041081A1 and US5702444A from Figure 7 and US7051654B2 from Figure 6,
these are all regarding organ or tissue printing of some description.
14
Section 5 – Conclusion
The patent families identified during this research of most relevance are detailed in
Appendix 2 below. From all the evidence gained from external sources and the patents that
have been found, it is clear that universities appear to be focused on developing methods
and conducting research with very few patents being published. The anomaly for this would
be Anthony Atala’s work at the Wake Forest Institute. The technical and technological
based side of the process is being carried out by major companies and they are creating
similar products, more focused on the machine rather than the process or biological
components, each with corresponding patents. However these patents claim to print viable
cells and then state that this can be applied to the production of organ transplants reducing
the relevance or usefulness of the patents to our research.
A number of new patents have been identified during this project, however, in keeping with
Mohsan Alvi’s conclusions we find that organ printing, particularly complex organs, is still in
its infancy and a distance from worldwide production, although important advances are
being made in the field.
15
References
[1] [http://www.gesim.de/en/bioscaffolder/]
[2] See Mohsan Alvi’s report. Page 7 Line 8
[3] [http://www.ted.com/talks/anthony_atala_printing_a_human_kidney]
[4] [http://3dprinterplans.info/china-develops-3d-bio-printer-called-regenovo-prints-a-liver-and-an-ear/]
[5] [http://regenovo.com/english/index.aspx]
[6] [http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-21328109]
[7] [http://roslincellab.com/storage/PresscoverageFeb2013b.pdf]
[8] [http://www.ib3.eps.hw.ac.uk/Will_Shu.html]
[9] For example see EP1896569A1
[10] [http://3dprint.com/7729/3d-print-organs-vascular/]
[11] [http://sydney.edu.au/news/84.html?newsstoryid=13715]
[12] [http://sydney.edu.au/dentistry/staff/profiles/luiz.bertassoni.php]
[13] [http://www.princeton.edu/main/news/archive/S36/80/19M40/index.xml?section=topstories]
[14] [http://www.engineering.cornell.edu/research/faculty/profile.cfm?netid=lb244]
[15] [http://www.news.cornell.edu/stories/2013/02/bioengineers-physicians-3-d-print-ears-look-actreal]
[16] [http://www.techrepublic.com/article/breakthrough-how-scientists-are-3d-printing-a-human-heartthat-will-work-better-than-yours/]
[17] For example US20100075293A1
[18] [http://www.upenn.edu/spotlights/rep-rap-3d-printing-blood-vessel-networks]
[19] US20120058174A1
[20] US8691974B2
[21] [http://www.sbes.vt.edu/people/bio.php?person=Paul-Gatenholm]
[22] Represented by WO2013040087A2, US20140093932A1 and US20140012407A1
[23] Represented by US6942830B2, EP2605805A2
[24] See table entries 1-15 in Appendix 2
[25] See table entries 16-20 in Appendix 2
16
Appendix 1 – Search Terms and Highlighted Patents
Keyword Search
(((((3 or three) adj (dim* or D))
or 3D or 3-D) near3 print*) or
bioprint* or (bio adj print*) or
biofabrication or (additive adj
manufact*)) and (organ or
organs or tissue or tissues)
Responses
76
Highlighted Patents
US20130004469A1
Engineered lumenized vascular
networks and support matrix
US20130017564A1
Bioprinting station, assembly
comprising such bioprinting
station and bioprinting method
EP2679669A1
Fabrication of threedimensional hydrogel objects
WO2013181375A1
Tissue repair devices and
scaffolds
WO2013040087A2
Platform for engineered
implantable tissues and organs
and methods of making the
same
US20140052285A1
Method for specifying and
fabricating an object,
associated apparatus, and
applications
WO2014039427A1
Methods of tissue generation
Appendix 2 - Final Patent Results
Publication
Title (English)
Number
US20140052285A1 Method for
specifying and
fabricating an
object, associated
apparatus, and
applications
WO2014039427A1 Methods of tissue
generation
Title - DWPI
Assignee/applicant
Machineimplemented
method for
specifying
target object i.e.
Living tissue,
fabricated by
threedimensional
printing
Forming threedimensional
tissue/organ
Cornell University, Ithaca,
NY, US
17
Anthrogenesis
Corporation, US
Application
date
2013-10-28
2013-09-03
US20140012407A1 Devices, systems,
and methods for
the fabrication of
tissue
US20130304233A1 Continuous digital
light processing
additive
manufacturing of
implants
US20140099709A1 Engineered threedimensional
connective tissue
constructs and
methods of making
the same
US20140093932A1 Devices, systems,
and methods for
the fabrication of
tissue utilizing UV
cross-linking
US20130017564A1 Bioprinting station,
assembly
comprising such
bioprinting station
and bioprinting
method
WO2013040087A2 Platform for
engineered
implantable tissues
and organs and
methods of making
the same
US20130164339A1 Platform for
engineered
implantable tissues
and organs and
methods of making
the same
Bioprinter for
fabricating
tissues e.g.
Connective
tissue and
organs
Making tissue
engineering
scaffold
Organovo Inc. San Diego,
CA, US
2013-08-15
Case Western Reserve
University, Cleveland, OH,
US
2013-07-26
New
engineered,
living, threedimensional
connective
tissue construct
comprising
connective
tissue cells
Bioprinter
useful for
fabricating
tissue construct
Organovo Inc. San Diego,
CA, US
2013-03-13
Organovo Inc. San Diego,
CA, US
2013-03-11
Bioprinting
station useful
for bioprinting
2012-09-17
New living,
threedimensional
engineered
tissue or organ
Organovo Inc. US
2012-09-12
New living,
threedimensional
tissue construct
Shepherd Benjamin, San
Diego, CA, US
2012-09-12
18
EP2679669A1
Fabrication of
three-dimensional
hydrogel objects
US8691974B2
Three-dimensional
bioprinting of
biosynthetic
cellulose (BC)
implants and
scaffolds for tissue
engineering
WO2012122105A1 Delivery system
US20120089238A1 Integrated organ
and tissue printing
methods, system
and apparatus
US20110250688A1 Three dimensional
tissue generation
US20090208466A1 Ink-jet printing of
tissues
US8691274B2
Inkjet printing of
tissues and cells
Preparing threedimensional
hydrogel
objects
comprising
living cells
Threedimensional
nano-cellulose
based structure
useful for tissue
regeneration
Eth Zurich,8092 Zurich,
CH,100816979
2012-06-26
Virginia Tech Intellectual
Properties Inc.
2012-03-28
Forming skin
tissue on
patient bodily
surface of
patient in need
Printing organ
or tissue in
many layers
Wake Forest University
Health Sciences, US
2012-03-05
Generation of
threedimensional
tissue construct
including
bladder
Improved
method of
forming an
array of viable
cells by ink-jet
printing
Printing cell,
e.g. Stem cell
apparatus
Immunotrex Corporation,
Lowell, MA, US
19
2011-10-06
2011-06-27
2009-04-23
Wake Forest University
Health Sciences, WinstonSalem, NC, US
2009-02-13
US20060105011A1 Method and
apparatus for
computer-aided
tissue engineering
for modelling,
design and
freeform
fabrication of tissue
scaffolds,
constructs, and
devices
US20060237880A1 Hydrogel constructs
using
stereolithography
Manufacturing
complex parts
or devices, such
as artificial
organ or tissue
scaffold
Fabrication of
hydrogel
construct
Board of Regents the
University of Texas
System, Austin, TX, US
2005-04-22
US7051654B2
Ink-jet printing of
viable cells
Formation of
array of viable
cells
Clemson University,
Clemson, SC, US
2003-09-17
US6942830B2
Device and method
for the production
of threedimensional objects
Producing 3dimensional
objects under
mild conditions
EnvisionTEC GMBH, Marl,
DE
2002-10-11
20
2005-09-26