Using hyaluronic acid to create a fetal-like environment in vitro

The fetal wound healing matrix is exceptionally rich in hyaluronic acid (HA). Fetal wounds heal without scarring or contraction. Noting these observations, we cultured adult dermal explants in the presence of various concentrations of medical-grade HA in vitro. In the presence of HA, fibroblasts migrated from the dermal explant and multiplied more rapidly than control explants. Subsequently, sterile toothpicks were used to disrupt (wound) fibroblast monolayers mechanically and the rate of closure was monitored. Cells cultivated in the presence of 5 mg/ml of exogenous HA changed in morphology and closed the wound more quickly than control cultures. Cells surrounding the wound extended numerous podalic processes and showed increased interdigitation. The effect of HA on cell proliferation is usually discussed in terms of the mechanical effects HA exerts on cells and the extracellular matrix. The physiological effect of HA may lie in its ability to act as an accessory receptor in cooperative ligand-binding pathways. For example, HA may bind growth and/or other factors, and thereby increase the effective concentration of these factors at the cell surface.