Biomedical Engineering Reference
In-Depth Information
Yannas, 2001). Data from these models clearly shows that blocking of contraction
is very probably required but it certainly does not suffice for regeneration.
These observations do not prove the existence of a cause-effect relationship
between induced regeneration and contraction blocking. Nevertheless, the indirect
evidence linking induction of regeneration and contraction blocking by active
scaffolds is extensive and currently forms a useful theoretical framework that best
explains the available data.
14.9
Mechanism of regeneration by use of scaffolds
Having highlighted the empirical evidence for an antagonistic relation between
contraction and regeneration in adults, we now seek mechanistic pathways that
account for such a theoretical relation. In particular, we focus below on cell types
that play a dominant role in wound contraction and identify mechanistic pathways
for blocking their contractile activity.
14.9.1
The contractile fibroblast (myofibroblast, MFB), is
most probably the main cell type associated with
wound contraction
The differentiated myofibroblast, referred to here simply as myofibroblast (MFB),
has been generally credited with generation of most of the contractile forces in skin
wounds (Rudolph
et al
., 1992; Desmoulière and Gabbiani, 1996; Lanning
et al
.,
2000; Tomasek
et al
., 2002; Thannickal
et al
., 2003). The specific feature which
provides the most useful operational distinction of MFB differentiation is expres-
sion of the
-smooth muscle actin phenotype (Tomasek
et al
., 2002). There is
considerable evidence that myofibroblast differentiation is regulated by at least
one cytokine (transforming growth factor, TGF-
α
1), the presence of mechanical
tension and an extracellular matrix component (the ED-A (extracellular matrix
component) splice variant of cellular fibronectin) (Desmoulière
et al.
, 2005;
Tomasek
et al
., 2002). The concurrent action of these factors appears to result in
a feedback loop, in which tension development facilitates TGF-
β
β
1 production and
activation of
-SMA expres-
sion increases tension development (Hintz
et al
., 2001; Tomasek
et al
., 2002).
There is strong evidence that credits TGF-
α
-SMA (smooth muscle actin) expression; in turn,
α
-SMA
expression, but also with modulation of bonding between adhesive receptors
(focal adhesions) and extracellular matrix molecules (e.g. ED-A fibronectin)
(Hintz
et al
., 2001; Hintz and Gabbiani, 2003; Serini
et al
., 1998; Thannickal
et al
.,
2003). An alternative view of the cell type involved in wound contraction has been
described (Ehrlich
et al
., 1999). In the discussion below it will be hypothesized that
myofibroblasts (MFB) are in fact the dominant cell type required for wound
contraction.
β
1 not only with induction of
α
