Biomedical Engineering Reference
In-Depth Information
values of
σ
range from about 40,000 at an average pore diameter of 20 µm down to
4000 mm
2
/mm
3
at a pore diameter of 200 µm (Chang 1988). The data show that an
upper limit for the pore diameter, estimated at 120 µm (Fig.
9.3
), corresponding to
a minimum specific surface of about 6000 mm
2
/mm
3
, is required; above this limit,
contraction delay became minimal, probably because, above this level, there was
insufficient specific surface to bind most of the contractile cells in the wound.
The degradation rate is optimized on a different basis. As mentioned above, the
proposed mechanism of contraction blocking requires adhesive contact between
integrins of contractile cells and ligands on the scaffold surface. Contractile cells
are expected to bind on the scaffold surface, thereby losing their axial orientation
and state (Fig.
9.1
) and becoming mechanically incompetent to apply a directed
contraction force. To accomplish this step, it is necessary for the cells to bind on an
insoluble (nondiffusible) scaffold surface. Such a solid-like surface “fixes” tempo-
rarily the cells in a randomized spatial orientation and also separates cells from each
other; a dissolved (degraded) scaffold would be diffusible and would be unsuitable
for stable fixation on the surface. Myofibroblasts appear in a full-thickness skin
wound at about 1 week following injury and disappear in about 3-4 weeks (possibly
due to apoptosis; Chap. 8). A scaffold that degrades with a half-life less than about
7 days would therefore be excessively degraded by the time it makes contact with
the relatively few contractile cells available in the wound at that time. On the other
hand, a scaffold with a half-life much longer than 3-4 weeks would not be able to
encounter a sufficient number of contractile cells in the wound either. The adhesive
cell-scaffold contact that contributes to contraction blockade can therefore be made
only during the critical window of opportunity between 1 and 3-4 weeks.
A requirement for finite density of ligands for integrins α1β1 and α2β1 is consis-
tent with the requirement for adhesive contact of contractile cells with the scaffold,
a prerequisite for contraction blockade. Although it seems plausible to hypothesize
that the active scaffold which blocks contraction efficiently (see above) owes its ac-
tivity to its superior ligand density, the data are limited to very few scaffolds and do
not provide basis for such a conclusion. The available data also preclude a quantita-
tive optimization of the ligand density. It is possible to make the case for existence
of a minimal ligand density, below which binding would practically disappear; and
of a maximal ligand density, limited by availability on the collagens structure. The
incomplete evidence supports a requirement for a finite ligand density on the scaf-
fold surface but provides no more information that could be used to set an optimal
value. In the absence of such information, it is suggested that a possible guideline
for ligand densities that exceeds 200 µΜ α1β1 or α2β1 ligands could be used until
further information becomes available.
A structural feature on the scaffold surface that might be responsible for the ob-
served significant reduction in TGFβ1 concentration in DRT-treated nerve wounds
(presumably by binding of the growth factor on the DRT surface, as described in
Chap. 8) is not apparent at this time.
The critical features of an active collagen scaffold that have been described
above appear to have a significance similar to the structural determinants of bio-
logical activity for proteins: they are required for regenerative activity to be present.
