Biomedical Engineering Reference
In-Depth Information
mechanically stable tissue. Split thickness graft was applied after the Laserskin
®
had almost completely biodegraded leaving a thin epidermal layer. As no controls
were included it is not evident whether a full epidermal layer, resistant to shear
forces, would have successfully developed without the STSG.
9.4 Summary
Fibrin- and hyaluronic acid-derived matrices are ideal candidates for the delivery
of keratinocytes. The most important role which any wound repair material plays
is in providing an environment in which cells of the correct tissue phenotype can
proliferate, differentiate and form an organised structure. In order to fulfil an
effective functional role, the final repair tissue is required to be as similar as
possible in structure and function to the native, undamaged tissue. A successful
repair tissue will contain most, or all, of the elements of the original tissue. In skin,
the establishment of a functional dermis and a viable basement membrane is key
to the formation of an organised and stable epidermis. The organised deposition of
proteins such as laminin 5 and collagen VII at the DEJ is known to be vital in
basement membrane formation (Breitkreutz
et al
., 2004).
It is well established that epithelium formed as a result of the application of CEA
is unstable (Desai
et al
., 1991). This instability is thought to be due in part to the
enzymatic treatment required to release the cell sheet from the tissue culture plastic
flask prior to clinical application. It could be postulated that enzymatic digestion
irreversibly damages the proteins forming the basement membrane such that a
subsequent establishment of a stable DEJ does not occur. The delivery of
keratinocytes which have been pre-cultured in or on a carrier matrix, such as
hyaluronic acid or fibrin, removes the need for enzymatic digestion and cells can
be delivered to the wound bed in a proliferative state with their extracellular
proteins intact. It could be speculated that keratinocytes delivered to the wound
bed in such matrices are better able to form a DEJ than keratinocyte sheets or
suspensions following enzymatic treatment. Clinical studies using such carrier
matrices have demonstrated their suitability as epidermal repair materials when
used in combination with cultured keratinocytes. Certain aspects, such as their ease
of handling, make them particularly attractive as repair materials. Few compara-
tive studies exist which directly compare these delivery matrices with other
treatments such as CEA, sprayed sub-confluent keratinocytes and sprayed sub-
confluent keratinocytes delivered in fibrin glue. As such, it is difficult to elucidate
which treatment provides the highest quality and most stable epidermis, and future
research should be directed towards establishing which combinations can be used
to achieve this. The studies described here of the use of fibrin and hyaluronic acid
carrier matrices for delivery of keratinocytes demonstrate that, as a mode of
delivery, this approach has huge potential. By further refining the physical and
chemical properties of the delivery matrix, such that a healthy and stable epidermis
is regenerated following skin loss, further improvements can be achieved.
