Biomedical Engineering Reference
In-Depth Information
2006). But because a complete characterization of native dermis is not available
and the composition of substitutes is known to affect healing outcomes (Shafritz,
et al.
, 1994), it is uncertain what material components and in turn biological
attributes, may be altered or missing in such devices. Thus, while TE products may
aid wound closure, they may not provide for fully regenerative outcomes. In
contrast, recent advances in processing techniques have permitted native tissues to
serve as starting materials for the production of acellular ECM scaffolds. Such
materials greatly aid researchers in their understanding of the factors necessary to
support regenerative healing while at the same time providing clinician and patient
with better wound care options.
In treating cutaneous wounds, RTM use translates to enhanced functional
outcomes by providing a thicker graft, thereby reducing wound contracture and
increasing patient mobility while maintaining graft take rates (DeClement, Jr.
et
al
., 1997; Lattari
et al
., 1997; Sheridan
et al
., 1998). These functional outcomes,
the result of biological properties that support fibroblast infiltration, neo-vasculari-
zation and epithelializaiton in the absence of inflammation, lead to increases in
overall cosmesis (Wainwright
et al
., 1996).
10.1.3
Concept of an acellular dermal matrix
The limitation of allograft skin as a viable treatment for skin loss results from cell-
based immunogenicity introduced as part of the graft. Removing all remaining
cells in the dermis renders a completely acellular dermal matrix that is essentially
immunologically inert and can serve as a general ECM scaffold for soft tissue
replacement. Furthermore, by starting with the native ECM, the resulting scaffold
retains much, if not all of the native dermal architecture and composition. Thus,
acellular dermal ECMs allow for successful engraftment of allogeneic dermis and
formation of fully differentiated skin without contracture (Heck
et al
, 1985;
Langdon
et al
., 1988). These studies further demonstrate the importance of the
dermal matrix in wound healing and its general low antigenicity.
During fetal development, wounds are believed to undergo regenerative healing
and the absence of scarring is noted. Thus, the human body has the intrinsic
capability to regenerate tissue. However, this capacity is lost during development
and replaced by a reparative scarring process (Adzick and Longaker, 1992).
Although the adult human heals by this reparative scarring process, in the absence
of some underlying dysfunction, the cytokines and pluripotent progenitor cells
necessary for regeneration are still available. Seemingly, the tissue in the adult
wound environment does not provide the proper chemoattractant and differentia-
tion signals necessary for a regenerative healing pathway. The provisional fibrin
scaffold deposited during hemostasis is distinctly different from the native dermal
matrix in composition, architecture and mechanical properties, all of which are
known to affect cellular responses. Therefore, the key component missing in adult
wounds is the native intact ECM scaffold. Such a scaffold, comprised of native
