Biomedical Engineering Reference
In-Depth Information
An efficient contraction blockade is mounted when these three structural param-
eters of DRT are present at optimal levels. In the presence of the active collagen
scaffold, the myofibroblast density is significantly reduced, the tight assembly of
contractile cells normally observed in healing wounds is dispersed, and the axial
orientation of cells becomes randomized. These profound changes in morphology
of contractile cells appear to explain adequately the observed cancellation or near
cancellation of the macroscopic force of wound contraction in the presence of the
scaffold. Specific binding of contractile cells on the temporarily insoluble scaf-
fold surface via integrin-ligand interactions as well as provision of a large enough
surface through optimization of the pore diameter partly account for the observed
contraction blockade. The scaffold half-life requires optimization as well in order
to make contact with contractile cells over the period, 1-4 weeks, when contractile
cells appear in the wound. Reduction in TGβ1 concentration is probably accounted
for by the observed high-binding affinity of the cytokine to the collagen surface.
Impaired wounds close without contraction but also without regeneration. These
examples include wounds in diabetics as well as pharmacologically impaired
wounds; also included are wounds that were mechanically splinted. These examples
of impaired healing show that a contraction blockade is not sufficient to induce
regeneration.
Although required in the presence of the collagen scaffold, a contraction block-
ade does not provide by itself for synthesis of new stroma or of epithelial tissue.
Stroma is synthesized by fibroblasts and differentiated fibroblasts in close contact
with the scaffold which appears to provide steric guidance for the synthesis of colla-
gen fibers. Somewhat speculatively, the new connective tissue is therefore a partial
topological replica of the scaffold. In the absence of the mechanical field of a nor-
mally contracting wound, the cells are disoriented and synthesize connective tissue
with collagen fibers that are largely oriented randomly in space, as in the physi-
ological dermis, rather than being highly aligned, as in scar. Synthesis of stroma
probably results from the interaction of two processes both of which provide spatial
cues: The scaffold acts as a spatial template that breaks up cell-cell binding and
instead binds cells on its surface, thereby assigning specific locations to the cells;
and by cancelling the mechanical field of contraction it leads to randomization of
axes of the cells that synthesize collagen fibers.
The two steps that comprise the overall process of induced regeneration, i.e.,
contraction blockade and stroma synthesis, have been shown capable of proceed-
ing independently, as shown in an island graft experiment using DRT (Orgill and
Yannas 1998).
Synthesis of the new epithelium is based on the spontaneous ability of epithelial
cells to induce regeneration of parent tissue provided stroma is present. If a suffi-
cient number of endogenous epithelial cells have survived the injury, they prolifer-
ate and mature into functional epithelial tissue using the surface of the new stroma
as a spatial guide (Chap. 5; see also below in section on decellularized matrices).
Other processes, not clearly understood at this time, lead to angiogenesis, neuro-
genesis, and completion of the remainder of regenerative processes for the organ.
