Biomedical Engineering Reference
In-Depth Information
limited but it would appear to have potential as an improvement on the current
delivery systems of CEA and sprayed cell suspensions.
Fibrin matrices have also been used for the delivery of growth factors. For
example
-FGF) was used to stimulate angiogenesis in
a rabbit ear ulcer model (Pandit et al. , 1998). In athymic mice the delivery of
epidermal growth factor (EGF) in combination with fibrin matrix and cultured
keratinocytes was found to improve generation of the dermal-epidermal junction
when compared with keratinocytes and fibrin alone. Little work has been under-
taken on the impregnation of cell carrier matrices with growth factors, although
these studies would suggest that improved epidermal stability and regeneration
could be facilitated by their use.
β
-fibroblast growth factor (
β
9.3 Hyaluronic acid and Laserskin ® as a repair
material
Laserskin ® is an epidermal membrane delivery system on which keratinocyte
cultures can be established and transplanted at sub-confluence ( Fig. 9.1 and Fig.
9.2) . The sheets are composed of hyaluronic acid (HA) and have regular sized,
circular, laser cut, microinterstices 40 µm in diameter that penetrate the 20 µm
depth of the material (Zacchi et al ., 1998). It can be used as an epidermal
replacement in combination with dermal replacements such as Integra ® and
Hyalograft-3D ® (Hyalomatrix ® ) or can be applied on its own when dermal ele-
ments remain.
Hyaluronic acid is a high molecular weight glycosamino-glycan (GAG) com-
posed of alternating glucuronic acid and N-acetylglucosamine residues found
naturally within the extracellular matrix. These groups are strongly hydrophilic
and therefore attract water and form a gel-like matrix. This turgidity provides
resistance to compressive forces whereas structural fibrous proteins resist ten-
sional forces.
There are four main groups of GAGs, determined by the linkage between sugar
residues and the number and location of sulphate groups. Hyaluronic acid is the
simplest of the GAGs and unique among them as it contains no sulphate groups and
is not found attached to proteins as a proteoglycan. Unlike other GAGs, which are
produced inside cells, hyaluronic acid is expressed from enzyme complexes
embedded in the plasma membrane. Hyaluronic acid is produced in large quanti-
ties during wound repair, allowing cell migration. During the repair process any
excess is degraded by the enzyme hyaluronidase.
HA is a major component of early granulation tissue. Fibroblasts in early
wounds produce more hyaluronic acid than fibroblasts in normal skin do. Hy-
aluronic acid has a stimulatory effect on wound healing and during proliferation
and regeneration hyaluronic acid concentrations are elevated, which allow cells to
migrate. Prior to mitosis, hyaluronic acid levels are elevated briefly, which allows
cells to dissociate. In addition to promoting proliferation, hyaluronic acid inhibits
 
 
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