Hyaluronic Acid Inhibits Fetal Platelet Function: Implications in Scarless Healing

Abstract Platelets are important for the initiation of inflammation in adults, but the role of fetal platelets in fetal wound healing is unclear because fetal dermal wounds heal with a minimal inflammatory response and lack of excessive scarring. Because fetal tissue is abundant in glycosaminoglycans (GAGs), predominantly hyaluronic acid (HA), this study was designed to test the hypothesis that HA inhibits the reactivity of platelets and thus contributes to the minimal scarring characteristic of fetal tissue repair. Platelets were isolated from 10 fetal pigs at day 80 of gestation (term, 115 days) and exposed to 0.5 mg/mL of arachidonic acid, an agent shown in prior studies to evoke maximal aggregation and degranulation of fetal platelets. The ability of HA at 0.1 and 0.5 mg/mL to inhibit this response was determind. The presence of HA resulted in a dose-dependent reduction in platelet aggregation at 180 seconds (control, 99.7 ± 0.3%; HA [0.1 mg/mL] 91.7 ± 3.8%; and HA [0.5 mg/mL] 48.5 ± 9.0%; P v control). The onset of aggregation was also significantly delayed by 0.5 mg/mL of HA (13.5 ± 2.5 seconds) compared to control (2.9 ± 0.7 seconds), P