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

Abstract

Background/Purpose: Collagen deposition in midgestation fetal skin wounds occurs rapidly and in a normal reticular pattern unlike adult scar. Although collagen types I, III, and V are present in both fetal and adult skin wounds, 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 days) and their ewes received subcutaneous polyvinylalcohol (PVA) sponge implants. PVA sponges were harvested at 3, 7, or 14 days after implantation, were processed, and then analyzed for collagen content, distribution, and corsslinking by two-dimensional cyanogenbromide (2-D CNBr) peptide mapping. Collagen 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 deposition within PVA sponges increased 25-fold in fetal lambs but only 10-fold in adult sheep. The type I to III ratios inside 14-day sponges of 75-day gestation 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 constituent. Although type V comprised less than 2% of normal skin collagen, α 1(V) chains constituted the greatest collagen fraction in 3-day fetal implants, whereas within 3-day adult sponges only α 2(V) collagen was detected. The total collagen content of unwounded fetal sheep skin increased twofold from 75 to 90 days' gestation. However, noncrosslinked forms of collagen type I diminished rapidly after 90 days' gestation, corresponding with the transition to scarring of fetal sheep wounds. Conclusions: Collagen types I, III, and V are deposited rapidly in fetal wounds and display an ontogenic transition in their metabolism from a fetal to an adult phenotype. Crosslinking of type I collagen increases during development and corresponds with the transition to scarring of fetal wounds after midgestation. These observations may help design strategies that induce a more fetallike repair of adult wounds.