Biomedical Engineering Reference
In-Depth Information
secondary wound have led to alternatives being sought in the development of
(CEA) and sprayed cultured keratinocytes.
The number of permanent, purely epidermal, biological skin substitutes pres-
ently available on the market is limited. Commercially produced autologous
keratinocyte sheets are available from a number of companies. The technology is
also available from a number of university and hospital laboratories and private
research facilities. The sheets are produced either on the surface of culture flasks
and then transferred onto a supporting delivery membrane, for example Epicel
®
, or
they are grown on a delivery material throughout the culture process, for example
Myskin
™
and Laserskin
®
(Moustafa
et al
., 2007; Ronfard
et al
., 1991).
The use of CEA alone to treat burns has provided inconsistent results, with
variable take rates and a tendency to blister (Desai
et al
., 1991; Woodley
et al
.,
1988). Sprayed keratinocytes derived from both sub-confluent cultures (Magnusson
et al
., 2007) and from uncultured cells isolated by the digestion of autologous split
thickness skin (Gravante
et al
., 2007) have been extensively used clinically.
Limited clinical data exist irrefutably proving which mode of keratinocyte delivery
provides the most effective wound closure. It is clear that a great deal of work is
still required to provide an environment in which keratinocytes or epithelial
precursor cells obtained from an autologous biopsy can grow into the highly
organised structure which constitutes a stable and fully functional stratified
epithelium.
9.2
Fibrin as a repair material
The use of fibrin glue in skin grafts and tissue engineered skin replacements has
been reviewed by Currie
et al
. (2001). Fibrin has been used as a haemostatic agent
and as a glue for the repair of tissue since the early 20th century (Bergel 1909)
although its effectiveness as a glue was only established 60 years later with the
introduction of a glue with a high fibrin content (Matras
et al
., 1972).
Commercially available fibrin sealants emulate the biological process of fi-
brinogen breakdown by thrombin to fibrin monomer and its subsequent
polymerisation in the presence of factor XIII and calcium to form fibrin polymer.
Numerous commercially available fibrin glues are marketed for use in a wide
variety of applications (Currie
et al.
, 2001; Eyrich
et al.
, 2006). Fibrin glues have
been used in cutaneous wound repair to improve graft adherence, to deliver
keratinocytes in suspension and for their delivery in a matrix or sheet form.
Wound healing progresses by a complex series of cellular and biochemical
interactions. These can be modified by providing an environment, in the form of a
matrix, in which these interactions are optimised to provide an increased rate of
healing with an improved and more stable final epithelial structure. For example,
the fibre size and spacing of fibrin fibrils within fibrin matrices has been shown to
affect the migration of fibroblasts into the matrix
in vivo
(Pandit
et al.
, 1998). The
ability to modify the structure of fibrin in the fibrin matrix, in order to provide
