HYALURONATE METABOLISM UNDERGOES AN ONTOGENIC TRANSITION DURING FETAL DEVELOPMENT - IMPLICATIONS FOR SCAR-FREE WOUND-HEALING

Wound healing in the fetus occurs by a different process from that in the adult. Instead of healing with scar formation, fetal cutaneous wounds heal by regeneration that results in complete restoration of normal skin architecture. The mechanisms responsible for this remarkable phenomenon involve factors in the fetal environment and properties intrinsic to fetal cells. Hyaluronic acid (HA) is a major component of the fetal extracellular matrix (ECM) and is believed to play an important role in this process. In this study, HA and HA-stimulating activity (HASA) in fetal and adult wound fluid were examined using sensitive, newly developed assays. In an ovine model, higher levels of HA and HASA were observed in fetal as compared with adult wound fluid. This difference was most prominent in wound fluid from fetal lambs at 75 and 100 days gestation (term=145 days); these samples contained persistently elevated HA and HASA levels for up to 2 weeks after wounding (HA peak levels 145 μg/mL and 110 μg/mL, respectively). In contrast, wound fluid from 120-day-gestation fetuses had significantly lower levels (P<.001) that were transient and similar to that in the adult (HA peak levels 70 μg/mL and 10 μg/mL, respectively). These observations confirm an ontogenic transition in wound HA metabolism from a fetal to an adult-like phenotype. Levels of HASA as a function of time after wounding correlated with levels of HA, suggesting a role for HASA in controlling HA deposition during tissue repair. Two patterns of HASA and HA synthesis were noted. Wound fluid from early and midgestation fetal lambs exhibited markedly elevated and sustained HASA and HA levels, and this pattern correlates temporally with the scarless wound healing response noted prior to 120 days gestation. In contrast, wound fluid from 120-day-gestation lambs and adult samples exhibited a small and transient increase in HASA and HA; this response correlated with the adult wound healing pattern that produced a scar. Thus, HA and HASA are both phenotypic markers for scar-free wound healing in the fetus, suggesting a mechanistic role for HA and other factors that regulate its deposition during the tissue repair process. These observations have important implications for devising new therapeutic agents to prevent scar formation. © 1993 W.B. Saunders Company. All rights reserved.