Relative distribution and crosslinking of collagen distinguish fetal from adult sheep wound repair

Background/Purpose: Collagen deposition in midgestation fetal skin wounds o ccurs rapidly and in a normal reticular pattern unlike adult scar. Although collagen types 1, III, and V are present in both fetal and adult skin woun ds, their relative distribution and pattern of crosslinking are unknown. We compared the quantity, distribution, and crosslinking of specific collagen types in fetal and adult sheep wounds. Methods: Nine fetal lambs at 75, 100, and 120 days' gestation (term, 145 da ys) and their ewes received subcutaneous polyvinylalcohol (PVA) sponge impl ants. PVA sponges were harvested at 3, 7, or 14 days after implantation, we re processed, and then analyzed for collagen content, distribution, and cro sslinking by two-dimensional cyanogenbromide (2-D CNBr) peptide mapping. Co llagen types were further analyzed in normal skin of fetal sheep at 75, 90, 125, and 140 days' gestation and in their ewes. Results: Between days 3 and 14 after implantation, total collagen depositio n within PVA sponges increased 25-fold in fetal lambs but only 10-fold in a dult sheep. The type I to III ratios inside 14-day sponges of 75-day gestat ion fetuses and adult ewes were 6.4 and 1.3, respectively. Thus, by day 14 in both fetal and adult sponges, type I collagen emerged as the major const ituent. Although type V comprised less than 2% of normal skin collagen, alp ha(1)(V) chains constituted the greatest collagen fraction in 3-day fetal i mplants, whereas within 3-day adult sponges only alpha(2)(V) collagen was d etected. The total collagen content of unwounded fetal sheep skin increased twofold from 75 to 90 days' gestation. However, noncrosslinked forms of co llagen type I diminished rapidly after 90 days' gestation, corresponding wi th the transition to scarring of fetal sheep wounds. Conclusions: Collagen types I, III, and V are deposited rapidly in fetal wo unds and display an ontogenic transition in their metabolism from a fetal t o an adult phenotype. Crosslinking of type I collagen increases during deve lopment and corresponds with the transition to scarring of fetal wounds aft er midgestation. These observations may help design strategies that induce a more fetallike repair of adult wounds. J Pediatr Surg 34:218-223. Copyrig ht (C) 1999 by W.B. Saunders Company.