Biomedical Engineering Reference
In-Depth Information
The evidence from peripheral nerve wounds is supportive of the deformation
theory of scar or neuroma formation (Yannas 2001b). In the presence of an inactive
collagen tube (e.g., silicone tube), the long axes of myofibroblasts inside the con-
tractile cell capsule are highly oriented along the circumferential direction; and so
are also the collagen fibers that are juxtaposed with the myofibroblasts, as observed
directly (Figs.
8.8
,
8.15
, Chamberlain et al. 2001a).
Other investigators have also emphasized the importance of mechanical fields in
scar formation in various organs (Fomovsky et al. 2012; Yang et al. 2013). Molecu-
lar implications of mechanical tension in development of scar have been pursued
(Leask 2013).
Theoretical treatments of scar formation have mostly neglected to account for
the mechanics of contraction. Alternative theoretical treatments have described the
quantitative interaction between cells and collagen fibers at a point in space with
various orientations, concluding that scar is determined primarily by the initial de-
position of collagen (Dallon and Sherratt 1998). A theoretical treatment based on
chemo-attractant gradients, hypothetically leading to increased collagen alignment,
has also been presented (McDougall et al. 2006).
The deformation field theory predicts that scar formation is a process derivative
to wound contraction during healing of wounds in adults. This theory contradicts
the commonly held view that scar formation can be used to explain why adults heal
their wounds spontaneously by repair, rather than by regeneration. We have seen
that the available processes for wound closure are just three, namely, contraction,
scar, and regeneration (Chap. 4). Further, the evidence presented above supports the
conclusion that scar formation is derivative to contraction. It follows that regenera-
tion in adults is primarily thwarted by contraction, not by scar formation.
8.4
Contraction Blockade and Regeneration Observed
in the Presence of Active Collagen Scaffolds
Collagen scaffolds can be prepared in homologous series of closely matched mem-
bers that can be used as internal controls of changes in their structural features.
These scaffolds make ideal probes of the mechanism of induced regeneration. A
few of them are particularly useful as reactants that block contraction while also
inducing regeneration.
A discovery that eventually pointed along an entirely new direction for a mecha-
nism of induced regeneration was first made in 1976 in my MIT laboratory (as-
sociated at that time with the Boston Shriners Hospital) with skin wounds. In a
frustrating sequence of experiments, it was observed that closure of full-thickness
skin wounds in guinea pigs was strongly delayed following grafting with a specific
collagen scaffold, rather than being accelerated, as demanded by the reasonable
clinical need. The new research direction resulting from that discovery was ex-
tended later to peripheral nerve wounds.
Over several years of study with animal models, it has been observed that wound
contraction in skin and peripheral nerves was almost entirely blocked when a
