Biomedical Engineering Reference
In-Depth Information
the STSG were not statistically different between the two groups, but tissue
thickness of the healing wounds above the subcutaneous fat was significantly
greater in the dermal RTM treated wound compared to the control group at all time
points up to 60 days postgrafting.
These initial results were independently confirmed and extended by assessment
of wound contracture and scarring (Reagan
et al
., 1997). Treating full-thickness
wounds with RTM and STSG significantly reduced contraction to 30.9% com-
pared to 42.9% for STSG treatment alone. Changes in degree of contraction were
noticeable by 6 weeks after grafting and persisted during the 10 week study. Blind
cosmetic analysis using a modified Vancouver assessment demonstrated a signifi-
cant reduction in scar value from nearly 12 to approximately 9.8.
In vivo
, cultured keratinocytes have also been shown to support responses
similar to STSG (Rennekampff
et al
., 1997). Furthermore, differential cell integrin
expression was observed to be a function of both wound healing time and the
formation of normal skin architecture. By 21 days after grafting, the laminin
binding integrin subunit
6 was exclusively observed on the basal side of basal
keratinocytes and the fibronectin binding integrin subunit
α
5 was not present.
These findings are consistent with the integrin expression differences witnessed
between normal and healing skin (Cavani
et al
., 1993; Grinnell, 1992; Hertle
et al.
,
1991) .
In vitro
studies have assisted in understanding the mechanistic processes
believed to support the
in vivo
responses described above. In particular, skin-like
organotypic cultures utilizing AlloDerm RTM as a dermal substrate have provided
insight into the microenvironmental factors and dynamic cross-talk between
epithelial and dermal components necessary for normal epidermal phenotypes and
skin morphogenesis (Andriani
et al
., 2003). AlloDerm seeded with fibroblasts
accelerated basement membrane (BM) assembly and supported both keratinocyte
growth and normalized epidermal architecture. However, AlloDerm cultures
lacking dermal fibroblasts exhibited slower assembly than when fibroblasts were
present. The role fibroblasts play in regulating matrix metabolism and keratinocyte-
produced BM components is likely to explain this result (Smola
et al
., 1998).
Cultures using neutralized collagen type I as the dermal substrate failed to support
BM assembly even in the presence of dermal fibroblasts, presumably owing to the
lack of BM components in the substrate. Thus, normal fibroblast phenotypes and
BM components are both necessary to support formation of normal stratified
epithelium. This study also demonstrates the potential limitation of
in vitro
experimentation.
Prior studies using AlloDerm employed cell seeding methods that do not
support normal infiltration of fibroblasts and therefore failed to mimic the
in vivo
condition (Ng,
et al.
, 2004). Methods that support uniform infiltration produced
distinctly different results (Andriani
et al.
, 2003). Similar issues arose when
fibroblasts were not included in the culture environments. Integrin expression of
keratinocytes cultured on AlloDerm
in vitro
(Rennekampff
et al
., 1996) was
α
