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RESEARCH
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Cytomechanics & Substrate
Guidance
Cell-level mechanical and 3D spatial cues are essential to the
organisation and architecture of new tissues as they form during
development, repair or in bioreactors. How these signals affect
organisation is key to both the basic understanding of tissue (particularly
connective and contractile) regeneration and tissue engineering
of implantable devices. The TREC has a long and unique track record
in both cell-generated forces (e.g. important in scar contracture)
and the mechanisms by which external mechanical loads control cell
behaviour and spatial organisation. The role of mechanical cues
in most cells can only be considered in conjunction with the mechanical
properties of cell substrate or scaffold are used. TREC has developed
a number of novel protein based cell scaffold materials to test
this linkage and provide cell level (microscale) guidance cues.
These have been based on liquid crystal, linear aggregating proteins,
fibronectin, fibrin, collagen. The group is now building up new
lab facilities to study and develop platform technologies based
on such meso-material substrates.
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3D Model Tissues & Tissue
Engineering Bioreactors
Work at the TREC for over 10 years has been directed to understanding
the control mechanisms and development of 3D tissue bioreactors.
These have chiefly used mechanical loading and cytomechanical
cues to control tissue formation. There are now a number of
versions of this system aimed at forming MODEL 3D tissues or
organoids in culture (models of nerve, muscle, tendon, skin,
gliding interface). These are all constructed on a similar pattern
but with differing cells/protocols, controlled by a defined
mechanical environment. These systems are not designed primarily
as therapeutic implants but to form MODEL TISSUES. Such models
are providing dramatic new insights into the detail of how simple
tissue systems grow and mature. Eventually they will form standardised
test beds for drug and device testing, pathological studies
and experimental platforms and tissue standards.
An important aspect
of this sector of study is the ability to quantitatively monitor
3D tissue properties (structure, cell activity, etc.) as it
changes with time. This is an active area, in collaboration
with colleagues in Medical Physics to develop and understand
minimally invasive signals from fibre optic spectroscopy, is
proving real-time structural information. This technology is
also being developed to monitor tissue architecture in vivo
using the tendon as a template model of organised, aligned structure
with gliding properties.
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Repair & Integration across Tissue Interfaces
TREC has a research theme studying specific questions of cell
matrix repair/regeneration, particularly across tissue interfaces,
both in reforming (integration) fixed anastomoses between cut
tissue surfaces (e.g. tendon laceration) or avoidance of adhesion
between interfaces which normally glide (e.g. tendon or nerve).
These are key basic questions in the reformation of a functional
tissue architecture needed for tissue regeneration. They also
directly impact on cell level mechanics within a tissue engineered
implant or repair site (See area 1). Understanding of the basic
mechanisms by which cells at interfaces either produce or prevent
actual physical (collagen/connective tissue) bridging is central
to functional tissue regeneration/engineering. TREC has a number
of novel experimental models and clinical translation research
projects to test potential therapeutic approaches.
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Network of Research
Interdisciplinary collaboration and networking are obligatory
to true tissue engineering or tissue regeneration. As a leading
research centre into basic control processing and platform systems
needed in tissue engineering, TREC is host to the British Tissue
Engineering Network (BRITE Net) and actively participates in
the UK and European Tissue Engineering Societies. In addition
TREC collaborates widely across the United States and Europe
with acknowledged centres of surgical, engineering and scientific
excellence in the field.
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