Although excellent esthetic and functional results can be achieved with post-natal cleft lip and palate repair, consecutive surgical procedures lead to scar formation and secondary midface growth retardation. This produces significant physical and psychological morbidity in cleft patients. The long-term objectives of this project are to develop a fetal model for cleft lip/palate to study the effects of intrauterine repair on wound healing and facial growth. Skin wounds heal in the intra-uterine environment without inflammation and scar. We hypothesize that in utero cleft lip repair will similarly result in healing by regeneration of oral mucosa, muscle and skin without inflammation and fibrosis. Secondary growth retardation of the maxilla will therefore not occur.
The specific aims of this study are: 1) To evaluate and refine a rabbit model for in utero cleft lip repair, 2) To determine if intrauterine repair results in healing by regeneration of oral mucosa, muscle and skin without scar and 3) To determine the optimal time for intrauterine repair. The experimental model has been developed in our laboratory. Time dated pregnant rabbits at 24 days gestation (mid-3rd trimester) are sedated and then anesthetized. One fetus per side of the bicornate uterus is exposed by hysterotomy. A paramedian cleft is created on one side of the lip and either repaired (in a straight line with 8-0 nylon sutures under 6X loupe magnification) or left unrepaired. Another fetus at a distance delivered by Caesarian section 24, 48, 72 and 96 hours postoperatively. Another group of fetuses will be euthanized at birth (5-6 days post-operatively). Wound healing will be evaluated by histological examination for inflammatory infiltrate, scar and regeneration of muscle, mucosa and skin. To further characterize wounds as adult or fetal, hyaluronic acid (HA) content of the wound will be quantitated at the same time points using a biotinylated HA probe. The experience and data gained from this preliminary investigation will be used to begin a comprehensive study to correlate the events of wound healing and facial growth after fetal cleft lip repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE009325-01
Application #
3425462
Study Section
NIDCR Special Grants Review Committee (DSR)
Project Start
1990-08-01
Project End
1991-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Dentistry
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Dodson, T B; Schmidt, B; Longaker, M T et al. (1991) Fetal cleft lip repair in rabbits: postnatal facial growth after repair. J Oral Maxillofac Surg 49:603-11