Biomedical Engineering Reference
In-Depth Information
Homeobox gene expression
Mechanistic differences between early fetal wounds and adult wounds are ulti-
mately regulated by a set of genes.
59,60
Collectively called homeobox genes, these
transcription factors are thought to regulate morphogenesis during development.
Eight of these genes (HOX-A4, HOX-A5, HOX-A7, HOX-B13, MSX-1, MSX-2,
MOX-1, PRX-2) are known to be expressed by normal fetal cells. Two of these
genes (PRX-2 and HOX-B13) are associated with scarless repair of early fetal
wounds. Following injury to fetal skin, fetal fibroblast expression of PRX-2 is
upregulated, coupled with HOX-B13 downregulation, thereby insinuating an
activation-deactivation mechanism (such that PRX-2 promotes regeneration and
HOX-B13 promotes scarring.)
4.6 Wound repair versus regeneration: fundamental
differences
Within the realm of wound healing, there is a subtle distinction between 'repair'
and 'regeneration'. Theoretically, all tissues are capable of repairing injuries.
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An
injury may be defined as an interruption of continuity of the morphology and/or
functionality of a given tissue. Repair, more specifically, refers to the physiologic
adaptation of an organ after injury, in an effort to re-establish continuity without
regard to exact replacement of lost/damaged tissue.
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True tissue regeneration
refers to the replacement of lost/damaged tissue with an 'exact' copy, such that
both morphology and functionality are completely restored. Unlike certain organ-
isms (such as newts), the organs of post-natal mammals do not regenerate
spontaneously. In some instances, such as skin, 'partial regeneration' may be
induced via use of exogenous agents, particularly biological matrices.
Currently, experimentally induced, regenerated skin tissue resembles normal
skin in form and function, yet it still lacks the presence of appendages.
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Neverthe-
less, the technology has immense value in clinical medicine and will be discussed
below.
Table 4.1
summarizes some key similarities and differences between
wound repair/scar formation and complete regeneration.
4.6.1 'Essential ingredients' for skin regeneration
As alluded to earlier, adult mammalian skin cannot regenerate spontaneously. As
a result, much of our understanding of how regeneration occurs has come from
models of scarless fetal healing.
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Using knowledge from those studies,
inferences can be made about the 'ingredients' necessary to promote tissue
regeneration in adult wounds. That is, for an adult wound to proceed towards a
regenerative pathway, its microenvironment (including exogenous materials)
must meet a set of criteria specific to regeneration.
Unlike regeneration, repair is considered the 'default' healing response, with a
