Hyaluronic acid is a major component of the matrix of fetal rabbit skin and wounds: implications for healing by regeneration.

The extracellular matrix (ECM) of fetal rabbit wounds contains an abundance of the glycosaminoglycan hyaluronic acid (HA) but is devoid of excessive collagen. Thus, fetal wounds heal without scarring, such that tissue repair grossly resembles regeneration. To obtain further insight into the process of fetal wound healing, the ECM of normal fetal rabbit skin was analyzed, thus providing a comparative endpoint for the ECM of healing fetal wounds. Similarities between the matrices would support the theory of healing by regeneration. The glycosaminoglycan (GAG) component of fetal rabbit skin from 24- and 29-day gestational age fetuses was extracted and then quantitated using an alcian blue binding assay. The extracted GAG was characterized by cellulose acetate electrophoresis and HA was identified by its selective digestion by Streptomyces hyaluronidase. The mean GAG content, measured as ng GAG per mg dry weight skin, was 260 +/- 200 for the 24-day group (n = 28) and 280 +/- 220 for the 29-day group (n = 26). The only GAG identified at both times of gestation was HA. This study has demonstrated that HA is the predominant GAG present in fetal rabbit skin and its quantity is stable during the period studied late in gestation. A major component of the ECM of both wounded and normal fetal skin is HA, indicating a close compositional similarity. These observations provide biochemical support for the hypothesis that the reparative process of injured tissue in the fetal rabbit proceeds in an attempt to reconstitute normality, i.e. regeneration.