Biomedical Engineering Reference
In-Depth Information
4
The pathophysiologic basis for wound
healing and cutaneous regeneration
D. T. NGUYEN, D. P. ORGILL
G. F. MURPHY
Brigham and Women's Hospital, USA.
and
Abstract:
In this chapter, essential aspects of cutaneous wound repair/scar
formation, including the early response and the cellular phase, will be
covered. Fundamental differences between wound repair and regeneration,
with emphasis on fibroblast and endothelial cell contribution to respective
dermal architecture, will be discussed. 'Essential ingredients' for cutaneous
regeneration will be explored in detail. Lastly, issues regarding stem cells,
progenitors and cellular 'plasticity', as they relate to cutaneous wound
healing, will be examined.
Key words:
fetal skin, regeneration, scar formation, stem cells, wound
healing, wound repair.
4.1 Introduction
Normal wound healing responses in post-natal human skin involve complex and
highly coordinated interplay among cells, soluble factors and an extracellular
matrix, with the ultimate goal of efficient and effective wound closure. Such
responses are likely to have evolved in
Homo sapiens
as a means of minimizing
intrusion across the cutaneous barrier by noxious and infectious environmental
agents that could threaten survival upon systemic dissemination. A fundamental
problem with this phenomenon, however, resides in the fact that this response
eventuates in a contractile scar that may impede normal function by limiting
motion (contracture) or by replacing essential tissue. Like seemingly more rudi-
mentary organisms, such as salamanders and planaria, which are capable of
regenerating complex tissue, the skin of the early human fetus responds to injury
via regeneration rather than scarring. Protected from the external environment by
normally sterile amniotic fluid, fetal skin can afford to employ the time, inherent
plasticity and coordinated differentiation programs necessary for a non-contrac-
tile, regenerative process. How fetal skin shifts from a regenerative response
in
utero
to a reparative post-natal response and how adult skin may be 're-educated'
to procede via a regenerative pathway instead of the wound repair-scar formation
pathway, is only now beginning to be explored.
In this chapter, the normal structural and functional complexities of human skin,
including biochemical and cellular events, implicit in physiological wound healing
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