Biomedical Engineering Reference
In-Depth Information
biological marker of deficient wound healing. Collagenase (such as MMP-8) and
elastase, secreted by neutrophils, are responsible for destroying connective tissue
and growth factors, respectively. Excessive use of exogenous corticosteroids,
malnutrition, radiation, infection and systemic disease are some causes of deficient
wound healing.
Typically seen as hypertrophic scars or keloids, excessive healing occurs when
collagen deposits in the dermis (and subcutis) far exceed the amount seen in a
typical scar.
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This is often preceded by an amplified inflammatory response with
the resultant overproduction of growth factors. Occasionally, excessive healing
can lead to scar contracture - pathological shortening of (completely re-epithelial-
ized and adequately healed) scar tissue (not to be confused with the physiologic
process of wound contraction, although the two may be related).
The clinical distinction between hypertrophic scars and keloids is that hyper-
trophic scars remain within the confines of the wound, whereas keloids extend
beyond wound boundaries.
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Relative to typical scars, fibroblast and myofibroblast
expression of TGF-
receptors are upregulated in keloids
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and thus collagen
levels are found to be 2-3 times higher.
18
Interestingly, compared to typical scars,
hypertrophic scars contain a higher subpopulation of myofibroblasts, yet keloids
appear to contain a significantly smaller myofibroblast subpopulation.
54
Histologically, it is not uncommon to find hypertrophic scars containing areas of
keloidal scarring, thus raising the possibility of a biological interrelationship.
Recent studies suggest that the development of hypertrophic scars and keloids are
associated with an increased presence of fibrocytes, especially in burn patients.
31,55,56
β
4.5
Comparison between fetal and post-natal skin
Presently, induced skin regeneration in adult mammalian wounds is partial rather
than complete. Secrets for constructing a microenvironment, such that injured
adult skin can be induced to regenerate fully, may lie in an in-depth understanding
of how fetal skin heals after injury. In general, human fetal skin wounded before
the third trimester has the capacity to heal without forming scars.
57-60
Hence, the
third trimester is thought to be the transition period, between regenerative fetal
healing and post-natal wound repair/scar formation. The ability of the early fetal
skin to regenerate an 'exact' copy of damaged/lost tissue is attributed to several
factors not seen in the adult counterpart.
4.5.1
Fetal environment and wound microenvironment
Fetal skin is bathed in an environment consisting of warm, sterile amniotic fluid that
is enriched with growth factors, hyaluronic acid and other ECM molecules.
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Nonetheless, such a sterile environment is deemed unnecessary for a regenerative
process to occur.
57
An example of this may be illustrated through the ability of a
marsupial fetus to heal without scars, while inside the mother's non-sterile pouch.
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