Biomedical Engineering Reference
In-Depth Information
9.5
Future trends
Tissue engineering approaches to skin wound closure have been in development
for over 25 years since the first reports of the use of CEA in the early 1980s.
Drawbacks including fragility, delay in availability owing to culture time, high
cost, uncertain take rate and poor mechanical stability have led to the development
of the current generation of biomaterials specifically designed for skin wound
repair. Owing to the nature of full thickness burn injuries these materials are
usually required to be seeded with epithelial cells or their precursors. The two
materials reviewed here are simple biological molecules and little work has been
undertaken substantially to modify their structure in order to improve their
function as skin repair materials. The primary goal in the development of epider-
mal replacement biomaterials should be to understand better how matrices such as
fibrin and hyaluronic acid can be further modified to provide a template for
organised tissue regeneration. The provision of the optimal environment for the
generation of the DEJ may be enhanced by altering the structure and/or the
functional groups of the carrier matrix. A material is required which provides an
element of wound closure whilst providing the optimal environment for keratinocyte
proliferation, differentiation, basement membrane formation and stratification of
the epithelium.
Previous experience with Integra
®
, de-epidermized dermis, Laserskin
®
and
fibrin suggests that modification of naturally occurring matrices is likely to be
more successful than totally artificial polymers in providing an effective matrix for
tissue regeneration. A combined approach is required with the employment of
modern polymer chemistry and fabrication technology to manufacture a material
which significantly outperforms other treatments. Other factors are important in
the development of such a material. Ease of handling and availability are vital as
is the time taken to produce the cell seeded matrix. The cost of the material is also
important.
The ultimate goal is to develop an epidermal repair material which is avail-
able 'off the shelf'. For this to be achieved, however, the use of allogeneic
material is a requirement, as a relatively large number of cells are required for
immediate delivery to the wound bed. Allogeneic keratinocytes have been
shown to treat partial thickness wounds in paediatric scalds successfully (Rab
et
al
., 2005). The provision of pre-made cryopreserved sheets of matrix containing
allogeneic cultured keratinocytes or keratinocyte precursor cells offers a poten-
tial solution, although the potential for rejection would need to be examined.
The seeding of such matrices with allogeneic pluripotent stem cells may provide
further advantages such that the transplanted cells differentiate in response to
environmental cues on the wound bed into a well organised epidermis. Such a
development could be combined with currently available dermal substitutes to
offer a viable co-cultured 'off the shelf' bilayered material. Initial studies have
indicated that such materials can be manufactured (Dai
et al
., 2005). However,
