Development and commercialisation of dCELL® Regenerative Biological Scaffolds for soft tissue repair
Submitting InstitutionUniversity of Leeds
Unit of AssessmentAeronautical, Mechanical, Chemical and Manufacturing Engineering
Summary Impact TypeEconomic
Research Subject Area(s)
Biological Sciences: Biochemistry and Cell Biology
Engineering: Biomedical Engineering
Medical and Health Sciences: Clinical Sciences
Summary of the impact
Novel biological scaffolds that regenerate with the patient's own cells
have been researched, and patented and since 2008 developed, taken through
successful clinical trials and commercialised. Economic impact within the
REF period has been delivered through the University of Leeds spinout
company Tissue Regenix plc, which has received £32M private investment,
employs 35 people and is AIM listed, with a capital value of £70M. Health
impact has been delivered through licensing and development by NHS Blood
& Transplant Tissue Services. The biological scaffolds have
demonstrated five years' successful clinical use in heart valve
replacement and three years' clinical use as a commercial vascular patch.
This case study is underpinned by multidisciplinary research led by
Professor J. Fisher in this UoA and Professor E. Ingham of UOA 5
at the University of Leeds. Fisher led the bioengineering aspects
of the research and is Principal Investigator on the grants (i)-(xi)
listed in section 3. Before 2000, soft tissue repair and replacement
primarily involved the use of synthetic biomaterials, chemically
cross-linked and inert bioprosthetic devices, autograft or allogeneic
donor tissues. Although these approaches are still used extensively, they
all have limitations.
Research in this area at the University of Leeds started in 2000. The
initial aim was to test the hypothesis that it was possible to develop a
regenerative biological scaffold, which, upon implantation, would
regenerate with the patient's own cells and provide tissue-specific,
multi-scale physical architecture. The objective was to develop a scaffold
to provide multi-scale biomechanical properties and function at the
macroscopic and cellular levels to support physiological function. The
scaffolds are designed to transform macro-scale physiological forces to
appropriate tissue specific micro-(cellular)-level strains to drive
appropriate cell differentiation.
The approach taken was to re-engineer native tissues through the
development of biochemical processes that removed the cells, cell
fragments and DNA to make them immunologically compatible without
compromising the tissue structure and architecture. The unique processes
created acellular biological scaffolds that retained the biomechanical
function and properties of the native tissue. The novelty of the process
was its use of very low concentrations of a detergent (sodium dodecyl
sulphate) and proteinase inhibitors in order to protect and maintain the
properties of the extracellular tissue matrix, coupled with a complete
wash-out of residual chemicals. The multidisciplinary research expertise
of the team enabled evaluation of both the biomechanical and biological
properties of the resultant regenerative scaffolds.
The initial scientific investigations in 2002 focused on heart valve
tissue, which comprises of a complex three-dimensional structure of thin
membranes [1, 2]. The research was funded by a local charity (grant i),
with clinical collaborators K. Watterson, Cardiac Surgeon at the Leeds
Teaching Hospitals Trust, and J. Kearney of NHS Blood & Transplant
Following the initial proof of scientific principle on heart valves,
research was then pursued with the backing of substantial EPSRC funding,
including a prestigious Portfolio Partnership Award for work on tissue
replacement and regeneration (grant iii). The research focused on
cardiovascular and musculoskeletal tissues and involved:
- Investigation of the functional biomechanics in 2005  and
recellularisation of scaffolds for heart valve applications
- The development of a bioprocess that allowed the development of the
dCELL® vascular patch  in 2006
- The development of further bioprocesses and the dCELL® biological
scaffolds for ligament and meniscus repair [5, 6] in 2007 and 2008.
The excellence of this research has been recognised by several external
awards: Fisher and Ingham, ERC Advanced Award (grant xi); Fisher,
CBE for services to Biomedical Engineering (2011); and the Queen's
Anniversary Prize for Higher and Further Education to the University of
Leeds, for its contribution to medical engineering.
Professor J. Fisher, Professor of Mechanical Engineering,
Professor E. Ingham (UoA5), Professor of Medical Immunology, 1990-present.
Fisher and Ingham have been supported by a team of research staff and PhD
References to the research
1. Booth C, Korossis SA, Wilcox HE, Watterson KG, Kearney JN, Fisher
J, Ingham E. Tissue engineering of cardiac valve prostheses I: Development
and histological characterisation of an acellular porcine scaffold.
Journal of Heart Valve Disease, 11; 457-462 (2002), PubMed ID: 12150290.
2. Korossis S, Booth C, Wilcox HE, Ingham E, Kearney JN, Watterson KG, Fisher
J. Tissue engineering a cardiac valve prosthesis II: Biomechanical
characterisation of decellularised porcine heart valves. Journal of Heart
Valve Disease 11; 463-471 (2002), PubMed ID: 12150291.
3. Korossis S, Wilcox HE, Watterson KG, Kearney JN, Ingham E, Fisher
J. In vitro assessment of the functional performance of the decellularised
intact porcine aortic root. The Journal of Heart Valve Disease 14; 408-422
(2005), PubMed ID: 15974537.
4. Mirsadraee S, Wilcox HE, Korossis KA, Kearney JN, Watterson KG, Fisher
J, Ingham E. Development and characterization of an acellular human
pericardial matrix for tissue engineering. Tissue Engineering, 12; 763-773
5. Ingram JH, Korossis S, Howling G, Fisher J, Ingham E. The use
of ultrasonication to aid recellularization of acellular natural tissue
scaffolds for use in anterior cruciate ligament reconstruction. Tissue
Engineering, 13; 1561-1572 (2007), DOI: 10.1089/ten.2006.0362.
6. Stapleton TW, Ingram J, Katta J, Knight R, Korossis S, Fisher
J, Ingham E. Development and characterization of an acellular porcine
medial meniscus for use in tissue engineering. Tissue Engineering Part A
14; 505-518 (2008), DOI: 10.1089/tea.2007.0233.
All of the above journals are internationally recognised with rigorous
review processes and international editorial boards. The quality of the
underpinning research being at least 2* is demonstrated by references 2, 5
Underpinning Research Grants (with Fisher as PI)
i) Fisher and Ingham. Children`s Heart Surgery Fund Leeds Tissue
engineering heart valves,. 2000- 2003; £248K.
ii) Fisher and Ingham. Ultrasonic modification of soft tissue matrices
for enhanced recellularisation EPSRC GR 59489/01; 2002-2003; £90K.
iii) Fisher and Ingham Portfolio Partnership; Tissue Replacement and
Regeneration; EPSRC GRS 63892/0; 2003-2008; £2.2M.
iv) Fisher, J. & Ingham, E. Development of small and medium diameter
vascular grafts Department of Health [HTD 430]; £421K ,01/10/07-30/09/10
v) Fisher, J., Ingham, E. et al. DTC Tissue Engineering &
Regeneration. EPSRC; £6M 1/10/08- 30/09/2015.
vi) Fisher, J., Ingham, E. et al. Functional Tissue replacement
and substitution: Platform Grant. EPSRC EPF0438721; £816K,
vii) Fisher, J. NIHR Senior Investigator Award. £60K, 4 years
viii) Fisher,J., Ingham, E. et al. Programme Grant: Biotribology
of cartilage and cartilage substitution EPSRC EPG01121721, £5.2M
ix) Fisher, J., Ingham, E. et al. Centre of Excellence in Medical
Engineering WELMEC, Wellcome Trust and EPSRC, WT088908/z/09/z, £11.2M;
five years 01/10/09-30/09/2014
x) Fisher, J., Ingham, E. et al. Innovation and Knowledge Centre.
Regenerative Therapies and Devices. EPSRC; EP G0324831, EPI0191031,
EPJ0176201 £10M, 01/10/09-01/10/14.
xi) Fisher, J., Ingham, E. Re-engineering and regenerating the knee. EU
ERC Advanced Investigator Award; €3M (€1.5M to this UoA, ref. 267114);
five years 01/04/11-31/03/16.
Details of the impact
Two strategic research challenges were identified for the research at
Leeds in 2000:
- To create regenerative biological scaffolds for cardiovascular tissue
repairs such as heart valves and cardiovascular patches;
- To create regenerative biological scaffolds for the repair of thicker,
three-dimensional musculoskeletal soft tissue such as ligaments, tendons
The unique approach taken at Leeds has generated tissue-specific
biological scaffolds and patents for each tissue repair application. This
contrasts with previous commercial biological scaffold approaches that
developed a single scaffold material with one set of properties and
applied it to many different applications. Failure to match site- and
tissue-specific properties can result in suboptimal physical performance
and regenerative response.
The commercial impact within the REF period has been enabled by
protecting the IP generated through the underpinning research in a number
of patents. The first patent [A] protected the basic process and
demonstrated its application in heart valves and pericardium. The patent
was filed prior to publication of the original research [1, 2] and is
supported by further research . The second patent [B] protected
processes for biological scaffolds for ligament regeneration and is
supported by the research at Leeds . The third patent family [C]
described biological scaffolds for meniscus regeneration and is supported
by the research at Leeds . The patents are owned and sustained by the
University of Leeds and have been licensed to Tissue Regenix plc for
commercial use and NHS Blood & Transplant Tissue Services for use on
allograft tissue within the NHS in the UK [A,B,C].
The University of Leeds spinout company Tissue Regenix was incorporated in
2006. Fisher was founding chairman and Ingham was founding
director. The corroborating statement [F], together with sources [D] and
[E], confirms that the impacts of the underpinning research, the patents
and the IP licensed to the company during the REF period has been as
follows. The original patent families were licensed into the company and
first-round investment was secured from IP Group in early 2007.
Second-round investment was secured in 2008 to support development and
manufacture of the first commercial product. A full-time chief executive
and new company chairman were appointed to lead commercialisation and take
the company to the market. Clinical trials were undertaken in 2009 on the
first commercial product, the dCELL® Vascular Patch, which was
CE marked as a Class III medical device and launched as a commercial
product in autumn 2010 [D]. The company was floated on the Alternative
Investment Market (AIM) as Tissue Regenix Group (TRG) in 2010 and, in
2012, raised further funds (£25M) to support development of a wider range
of commercial products for cardiovascular and musculoskeletal
applications. TRG`s market CAP, at a share price of 11p, is £70M (2012
valuation) and it is investing over £32M of private capital in new product
development, currently employing 35 people [D,E,F]. The University of
Leeds is a shareholder and investor in TRG. Fisher and Ingham are
shareholders and scientific advisers to the company.
The dCELL® Vascular Patch is now sold throughout Europe [E]. A
second commercial product, the dCELL® Meniscal Repair device,
is being developed, with clinical trials planned for 2014 [F]. A third
commercial product, a biological scaffold for ligament repair, is now in
commercial development. The University continues to collaborate with the
company and supports commercial development of products through its
Innovation and Knowledge Centre in Medical Technologies-Regenerative
Therapies and Devices (IKCRTD, grant x).
The University has contributed highly skilled personnel to Tissue Regenix
Group, with Leeds PDRA Graindorge employed as chief operating officer and
Leeds PDRA Berry, née Wilcox, working as the company's chief
scientist (co-author on [1,2,3,4]).
Statement [F] confirms that the dCELL® Vascular Patch has
completed a successful clinical trial, been CE marked and is bringing
benefits to patients undergoing endarterectomies for peripheral vascular
disease . Source [G] confirms that clinical studies using the
technology have been reported for heart valve replacement by the
researcher collaborators in Brazil, with improved outcomes at four years
for pulmonary valve replacements.
Statement [H] confirms that NHS Blood & Transplant Tissue Services
has licensed the technology for creating biological scaffolds from
allogeneic tissues. They are currently undertaking clinical studies on an
acellular biological scaffold for dermal repair, with initial results
already reported, and are investing in collaborative development projects
on cardiac patches, acellular heart valves, acellular vascular grafts and
acellular ligaments supported by translation projects through IKCRTD.
Sources to corroborate the impact
A. Fisher J, Ingham E, Booth C. Decellularisation of tissue implant
material. UK Patent Application GB 2375771 A (2002).
B. Ingham E, Fisher J. Ultrasonic modification of soft tissue matrices.
International Patent Application PCT/GB2004/002055, 2004. International
publication number WO 2004/103461.
C. Ingham E, Fisher J, Stapleton T, Ingram J. Preparation of tissue for
meniscal implantation. Patent Application PCT/GB2007/004349, 2008.
International publication number WO 2008/059244 A3.
(accessed December 2012)
(accessed December 2012)
F. Individual written corroboration from Managing Director, Tissue
Regenix, on the influence that this UoA's research has had on the
development of Tissue Regenix Group.
G. da Costa FDA, Santos LR, Collatusso C, Ingham, E. Thirteen years`
experience with the Ross operation. Journal of Heart Valve Disease. 18;
84-94 (2009), PubMed ID: 19301558.
H. Individual written corroboration from Head of R&D NHS Blood and
Transplant Tissue Services on the influence that his UoA's research has
had on the development of tissue products for patient use in the NHS.