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In-Depth Information
of these grafts (low “take”) and the low long-term durability of the outcome (Wood
et al. 2006; Atiyeh and Costagliola 2007; Fang et al. 2013).
In summary, the data showed that avulsion of KC sheet grafts was caused by
a critical structural flaw: the lack of a mechanically competent bond between the
anchoring fibrils and collagen fibers in the subepidermal layer. Most studies dis-
cussed above showed that anchoring fibrils were in fact synthesized underneath
the keratinocyte sheets that had been grafted on a dermis-free defect; in contrast, a
well-vascularized, thick dermis was not synthesized. The structural defect respon-
sible for avulsion could therefore be lack of synthesis of the dermis. In other words,
the adhesive joint may have failed mechanically because one of the two adhints (the
dermis) was either missing or, at least, was inadequately synthesized. In contrast, a
sufficiently dense mass of collagen fibers, which normally becomes enmeshed with
the anchoring fibrils of the BM, is present both in normal skin and in epithelialized
dermal scar, thereby preventing mechanical failure in either tissue structure.
This conclusion was further supported by a number of studies in which, prior
to being grafted with KC sheets, the full-thickness skin wound was grafted with
either a dermal allograft or a collagen scaffold that induces synthesis of dermis.
In early studies dermal allograft was grafted on full-thickness skin wounds in ani-
mals or humans with thermal injuries, followed by removal of the necrotic allograft
epidermis by abrasion several days later and resurfacing the exposed dermis with
a suspension of disaggregated syngeneic KC. No graft loss was observed in these
studies (Heck et al. 1985; Cuono et al. 1986, 1987; Langdon et al. 1988). It was
reasoned that removal of the epidermis from the allograft eliminated most of the
cells expressing alloclass II antigens, leaving behind a viable allogeneic dermal bed
that successfully integrated KC cultures without rejection (Cuono et al. 1987). We
note these studies among the first using decellularized matrices to circumvent the
problem of organ rejection. Many more studies with decellularized matrices have
been performed since then with a variety of organs, as described in a later chapter.
In later studies KC suspensions were replaced with cultured epidermal autografts
(CEA) that were placed over dermal allografts with similar positive results (Hick-
erson et al. 1994; Sheridan et al. 2001; Sood et al. 2010; Fang et al. 2013). Further
support to the hypothesis that cultured epithelia autografts require a dermal bed in
order to prevent avulsion was provided in a study where the dermal bed was synthe-
sized in situ with the dermis regeneration template (DRT) rather than allografted.
In this study, avulsion of KC sheets was not observed in the presence of DRT; in
contrast, KC sheets were avulsed after being grafted on a DRT-free and dermis-free
defect (Orgill et al. 1998).
5.2.6
Synthetic Potential and Limitations of Keratinocyte Sheet
Grafts
The literature of KC sheet grafting has been strongly focused on formation of a
highly differentiated epidermis and a complete BM underneath the epidermis in
dermis-free defects. The majority of evidence supports the conclusion that the BM,
