Abstract
The development of scarring following accidental injury or surgery is an important clinical problem, often resulting in adverse effects on frowth and function, as well as an undersirable cosmetic appearance. Adult wound healing and scar formation are characterised by acute inflammation, wound contraction and disordered collagen deposition. Similar processes may also be involved in the progression of fibrotic disease states such as pulmonary fibrosis and hepatic cirrhosis. A major clinical objective is therefore, the reduction, and ideally the prevention, of scarring. The embryo and early fetus respond to injury in a way that is fundamentally different from the adult. In general, the early fetus heals rapidly, without scar formation. Extracellular matrix deposition in the fetal wound is rapid and organised in its structure, much more similar in appearance to unwounded skin, whilst, in the adult, matrix deposition is disordered. The inflammatory response, charasterisitic of the early phase of adult wound healing, is absent, or highly limited, in the fetus and the levels of cytokines are generally greatly reduced. Research into fundamental cellular and molecular differences between adult and fetal wound healing have revealed a number o targets in the adult wound which can be manipulated to more closely resemble the fetal wound environment and hence result in the reduction of adult scarring.
Highlights
The development of scarring following accidental injury or surgery is an important clinical problem, often resulting in adverse effects on growth and function, as well as an undesirable cosmetic appearance
The transition from the scar-free to the scarring phenotype occurs between days 18 and 19 of gestation (Ihara et a/., 1990). in the mouse between days 16 and 17 (Whitby and Ferguson, 1991a) whilst, in the sheep. this transition occurs between days 100 to 120 (Longaker et al, 1990a)
The change from scarfree healing to the scarring phenotype of the adult is gradual in primates and in the rhesus monkey Lorenz and colleagues (1993) described a 'transition wound' between 85 and 100 days' gestation. in which wounds healed with an absence of sebaceous glands and hair follicles, but with reticular dermal collagen architecture similar to unwounded dermis
Summary
One of the most obvious differences between adult and fetal wound healing is the environment in which the wound heals. Human amniotic fluid has al$o been shown to inhibit the activities of hyalur@nidase, elastase and cathespin B, whilst enhanding collagenase activity (Gao et nl., 1994) These findings may, in part, explain the high levels pf HA found in fetal skin and the increased collagGnase activity may have a role to play in the superidr collagen fibre organisation seen in fetal wound healing. Wounds in adult sheep skin grafts on early gestation fetal lambs healed with the formation of a scar, whilst fetal-fetal transplants did not scar (Longaker et al, 1994) These investigations demonstrated that the fully differentiated skin of the adult cannot be modulated to heal in a scarfree fashion by perfusion with fetal serum or exposure to amniotic fluid. Increasingly complex dermal structure, cellular differentiation and immune system maturity all correlate with the diminishing ability to heal without scarring with increasing gestational age
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