This project will focus on the role of hyaluronidase and hyaluronidase inhibitors in fetal wound healing. The fetal wound has the unique ability to heal without inflammation and scar formation. Hyaluronic acid (HA) is prominent in the extracellular matrix whenever rapid tissue proliferation, regeneration and repair occur. This is the situation in the early stages of postnatal wound repair, prior to scar formation. In the postnatal wound, elevated levels of HA occur early but are transient, due to the appearance of wound hyaluronidase. In the fetal wound, however, the elevated HA levels are prolonged. Since HA inhibits cell differentiation, its prolonged presence in the healing fetal wound may explain the lack of scar formation by the fetus. This study will examine differences between repairing adult and fetal wounds in the rate of degradation of HA. We hypothesize that this rate of degradation is modulated by wound and serum hyaluronidase, possibly mediated through the presence of a hyaluronidase inhibitor. This study will develop sensitive and convenient assays to determine hyaluronidase and hyaluronidase inhibitor levels in adult and fetal sheep wounds as a function of time after wounding and gestational age. In addition, we will purify and characterize hyaluronidase inhibitor from fetal serum. The understanding and application of the mechanisms involved in this lack of scar formation would be of obvious use to all surgical specialties.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Unknown (K15)
Project #
5K15DE000307-05
Application #
2128718
Study Section
NIDCR Special Grants Review Committee (DSR)
Project Start
1991-02-01
Project End
1996-03-31
Budget Start
1995-02-01
Budget End
1996-03-31
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Stern, M; Dodson, T B; Longaker, M T et al. (1993) Fetal cleft lip repair in lambs: histologic characteristics of the healing wound. Int J Oral Maxillofac Surg 22:371-4
Afify, A M; Stern, M; Guntenhoner, M et al. (1993) Purification and characterization of human serum hyaluronidase. Arch Biochem Biophys 305:434-41
Stern, M; Stern, R (1992) An ELISA-like assay for hyaluronidase and hyaluronidase inhibitors. Matrix 12:397-403