Biomedical Engineering Reference
In-Depth Information
14.8.3
Blocking of contraction by use of templates in adult
mammals: induction of regeneration of skin,
conjunctiva and peripheral nerves.
Skin was the first organ to be induced to regenerate. Wound contraction was
blocked for over 25 days, a dramatic delay, when the unseeded DRT was grafted
onto full-thickness skin wounds in the guinea pig (Yannas, 1981; Yannas
et al
.,
1989). When the cell-seeded scaffold was grafted, contraction was not simply
delayed but arrested; the wound closed by simultaneous regeneration of a dermis
and an epidermis over most of the wound area (Yannas
et al
., 1981, 1982a,b,
1989).
Contraction was also blocked when DRT was grafted onto a full-thickness
wound in the conjunctiva, produced by excision of stroma (analogous in depth
of injury to a full-thickness skin wound; Tenon's capsule was also excised) in a
rabbit model (Hsu
et al
., 2000). Ungrafted wounds closed by contraction and
formation of scar tissue, the latter comprising an aligned array of dense collagen
populated by occasional fibroblasts. Grafting with cell-free DRT resulted in
regeneration of the conjunctival stroma, followed by spontaneous epithelializa-
tion of the stroma (Hsu
et al
., 2000).
Further incidence of contraction blocking coinciding with induced regeneration
was observed in studies of a peripheral nerve, the fully transected rat (or mouse)
sciatic nerve. This is a standard assay for regeneration studies in the peripheral
nervous system. The two nerve stumps, separated by a gap of controlled length, are
typically inserted inside a tube fabricated from an experimental material (Lundborg
et al
., 1982). In early studies, it was repeatedly observed that, following transec-
tion, the cross-section area of the distal nerve stump eventually was reduced by as
much as 50-60% (Holmes and Young, 1942; Sunderland, 1990; Weiss, 1944;
Weiss and Taylor, 1944). Later, significant evidence showed that regeneration was
marginal, with the incidence of neural scar, when the regenerated nerve connecting
the stumps was under substantial radial compression; in contrast, a very high
quality of nerve regeneration with negligible incidence of neural scar was ob-
served when compression of the regenerate was cancelled out. Contraction blocking
was observed to depend strongly on the use of highly porous collagen-GAG
(glycosamino-glycan) scaffolds with a defined structure (Chamberlain
et al
.,
2000; Harley
et al
., 2004; Yannas, 2005b).
However, data from studies of impaired healing (e.g. diabetic wounds, wounds
in obese animal models) show a different picture; although impaired healing in
adults is accompanied by loss of contraction, regeneration is not observed.
Experimental study of several models of impaired healing of skin wounds has been
based on use of pharmacological agents (e.g. steroids), controlled infection,
mechanical splinting, or on animal models of genetically impaired healing, such as
the diabetic mouse or the obese mouse. In all of these models contraction was
blocked almost completely, yet, regeneration was not induced (see review in
