title: Hyaluronic acid degradation products induce neovascularization and fibroplasia in fetal rabbit wounds.
abstract: Scarless fetal wound healing occurs with mild fibroplasia and neovascularization, while the wound is persistently enriched with hyaluronic acid. Conversely, adult wounds are characterized by prominent fibroplasia, neovascularization, and scar formation, and hyaluronic acid is a transient component of the early adult wound matrix. Our group has reported that enzymatic degradation of fetal rabbit wound hyaluronic acid results in marked increases in fibroplasia, collagen deposition, and neovascularization. This altered, adultlike healing response is hypothesized to have resulted from the generation of biologically active hyaluronic acid degradation products. Therefore, this study analyzes the fibrovascular inductive activity of hyaluronic acid degradation products. Fetal rabbit wounds were treated with hyaluronic acid degradation products generated by methods known to produce oligosaccharides with significant angiogenic activity. Implants from wounds treated with either of the control solutions (n = 4 for each control) had identical histologic features characterized by a mild mononuclear cell infiltrate but neither infiltrating fibroblasts nor collagen. In marked contrast, implants from wounds treated with hyaluronic acid degradation products contained infiltrating fibroblasts and collagen intermixed with numerous blood vessels. Quantitation of capillary ingrowth showed a sixfold increase in the neovascular response in wounds treated with hyaluronic acid degradation products compared with either controls (p < 0.05). This study shows that hyaluronic acid degradation products stimulate neovascularization and fibroplasia in fetal wounds. These observations suggest that a balance between hyaluronic acid accumulation and degradation has significant regulatory influence in fetal tissue repair.
authors.affiliation: The Wound Healing Center of the Division of Plastic and Reconstructive Surgery, University of Pittsburgh, PA, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Mast
authors.forename: F W
authors.initials: FW
authors.lastname: Frantz
authors.forename: R F
authors.initials: RF
authors.lastname: Diegelmann
authors.forename: T M
authors.initials: TM
authors.lastname: Krummel
authors.forename: I K
authors.initials: IK
authors.lastname: Cohen