HYALURONIC-ACID MODULATES PROLIFERATION, COLLAGEN AND PROTEIN-SYNTHESIS OF CULTURED FETAL FIBROBLASTS

Fetal wound healing is characterized by minimal inflammation, mild fib roplasia and rapid, but organized collagen deposition such that scarri ng is not apparent. The matrices of fetal wounds differ greatly from a dult wounds in that fetal wounds are persistently enriched with hyalur onic acid (HA). It has been shown that a reduction in fetal rabbit wou nd HA results in an adult-like healing response with increased fibropl asia and neovascularization. These observations suggest that HA can mo dulate cellular activity in fetal repair. Therefore, this study was de signed to define the effect of HA on fetal fibroblast function. Fibrob lasts from the skin of fetal rabbits were isolated and maintained in c ulture medium containing either no HA (controls), 1 mug/ml, 10 mug/ml or 100 mug/ml of HA (n = 6 for each group). Fibroblast proliferation w as quantitated by DNA content in each culture, and collagen and noncol lagen protein synthesis were analyzed by incorporation of [H-3] prolin e into collagenase-digestible and collagenase-nondigestible protein, r espectively. At all concentrations tested, HA significantly inhibited fetal fibroblast proliferation (p < 0.02), but stimulated collagen (p < 0.002) and noncollagen protein (p < 0.005) synthesis. These findings provide further evidence that HA affects the function of fetal fibrob lasts. Moreover, this study in conjunction with previous in utero find ings suggests that HA may have a regulatory influence in scarless feta l healing by affecting cellular function during the repair process.