Biomedical Engineering Reference
In-Depth Information
showing that such an association is not necessary. This conclusion comes out of sev-
eral studies of impaired healing of skin wounds in animal models, i.e., wounds that
were deliberately treated in a variety of ways that induce healing under pathologi-
cal conditions. Examples are wounds in animals treated with steroids (Billingham
and Russell 1956; Cuthbertson 1959: McGrath 1982), deliberately contaminated
wounds (Fiddes et al. 1991; Hayward et al. 1992) as well as wounds in genetically
diabetic animals (Greenhalgh et al. 1990; Klingbeil et al. 1991) and in genetically
obese animals (Klingbeil et al. 1991). These skin defects showed greatly delayed
contraction yet there was no evidence of regeneration reported in any of these stud-
ies of impaired healing.
Mechanical splinting has occasionally been used to control contraction of
skin defects. In a well-documented study, a modest delay in contraction of
dermis-free defects in rats was reported as a result of particularly effective
splinting; however, the defects eventually closed almost completely by con-
traction to the same extent as in the unsplinted control (Kennedy and Cliff
1979). Modest delays in contraction were reported to result from mechanical
splinting in other studies of dermis-free defects as well; however, contraction
resumed after the splint was removed and played a dominant role in wound
closure, as with unsplinted defects (Lindquist 1946; Abercrombie et al. 1960;
Zahir 1964; Stone and Madden 1975). In conclusion, there appears to be no
evidence that inhibition of contraction by mechanical splinting induced regen-
eration of the dermis.
8.5
Summary Conclusions on the Relation Between Wound
Contraction and Regeneration
The collection of data presented previously shows that there is an extensive factual
basis for hypothesizing an antagonistic relation between contraction and regenera-
tion, both in skin and peripheral nerve defects.
Spontaneously healing skin wounds in different species provide the first set of
data that support the hypothesis of an antagonistic relation between contraction and
regeneration. Evidence is presented from a study of the developing tadpole, where
contraction and regeneration appear to be mutually exclusive processes of wound
closure (Yannas et al. 1996); the well-known example of skin wounds in the rab-
bit ear where contraction is practically excluded due to tight binding between skin
and cartilage, and where regeneration of skin is observed (Joseph and Dyson 1966;
Goss 1980, 1992; Goss and Grimes 1972, 1975; Mustoe et al. 1991); studies of
regeneration of the injured oral mucosa in mice showing greatly reduced scar for-
mation (Schrementi et al. 2008; Mak et al. 2009; Wong et al. 2009; Larjava et al.
2011; Glim et al. 2013), while studies with swine showed that the oral mucosal
wounds contracted significantly less than the skin wounds (Mak et al. 2009) or else
showed lower levels of TGFβ1 and TGFβ1 expression than in control skin wounds
(Schrementi et al. 2008); studies with full-thickness excisional skin wounds in the
