Biomedical Engineering Reference
In-Depth Information
14.9.2 Biologically active scaffolds (regeneration templates)
appear to block contraction by interfering with the
number and organization of myofibroblasts
We start with a simple mechanical model of the macroscopic contractile force that
closes wounds in skin, conjunctiva and peripheral nerves. The macroscopic force
for contracting a skin wound spontaneously is estimated at about 0.1 N (Yannas,
2005b). An individual dermal fibroblast in culture is capable of developing a force
of the order of 1-10 nN (Freyman
et al
., 2001a,b, 2002). The number of contractile
fibroblasts required to develop the macroscopic force that suffices to close the
wound is, therefore, at least 10
-1
N/10 nN = 10
7
cells, suggesting a factor of this
magnitude to scale up the contractile force from cell to organ.
Scaffolds do not block wound contraction by mechanical splinting action. This
has become abundantly clear following observations of a series of scaffolds that
differed only in pore size but were otherwise identical in structure and in Young's
modulus (mechanical stiffness). A homologous series of scaffolds, all with a pore
volume fraction of 99.5% and with nearly identical mechanical properties, was
studied (see example in
Fig. 14.2(a
)). Only scaffolds in the pore size range 20-120
µm blocked contraction; scaffolds with a pore size outside this range did not (Fig.
14.2(b); Yannas
et al
., 1989). If splinting is a viable mechanism for scaffold
activity, scaffolds with identical Young's moduli but differing only in pore size
should not show such divergent behavior: all scaffolds, irrespective of pore
diameter, should block contraction. This is clearly not observed. Other data that
indicate that mechanical splinting is precluded as a mechanism of scaffold activity
are observations that Young's moduli for these scaffolds are a very low 200 Pa
(wet state; Harley, 2006), owing primarily to their very high pore volume fraction
of 99.5% (Fig. 14.2(a)). A simple calculation shows that such stiffness values are
orders of magnitude lower than necessary to provide the scaffold with any
significant mechanical splinting capability inside the wound.
In a simple model of an anatomically well-defined skin wound, contraction
results from a plane stress field that is generated by contractile cells with their
contractile axes lying in the plane of the wound (Yannas, 2001). The macroscopic
force vector,
F
c
, is considered to be the product of three contributions: the total
number of MFB in the wound,
N
, the fraction of cells bound to the matrix and
capable of applying traction,
, and the average contractile in-plane force vector
generated per MFB, expressed as
f
i
(Yannas, 2005b):
F
c
=
N
ϕ
ϕ
f
i
(14.2)
Two major mechanisms appear to account for reduction of the macroscopic
contractile force
F
c
by scaffolds. The first mechanism depends on reduction of the
number of MFB,
N,
while the second depends on reduction of the effectiveness of
forces generated by MFB in the wound.
Persistent observation shows that, in skin wounds that heal primarily by induced
