The long-term goal of this research is to develop treatment methods for the management of scar formation in tissues of the oral cavity based on understanding the mechanisms involved in wound healing of fetal and adult tissues. Peptide growth factors, modulated by the extracellular matrix (ECM), have been implicated in wound healing mechanisms in both animal models and human studies. The transition from scarless wound healing of the fetus to adult wound healing takes place gradually from early in gestation to birth, and is thought to be characterized by differences in spatial, temporal and quantitative relationships of growth factors and ECM components. We propose to study these changes in the localization and effects of peptide growth factors and clarify their effects on scar production during wound healing in the palate. To test the hypothesis that peptide growth factors mediate wound healing in developing fetal palatal tissues and their effects are influenced by the composition of the extracellular matrix, we will identify and characterize differences the spatial and temporal relationships of these growth factors and ECM constituents in developing mouse palate in organ culture. The effects of manipulating the cell microenvironment on wound healing and scar production will be evaluated by biochemical quantitation and characterization of fetal and adult collagen types and synthesis. Ultrastructural characterization of wound architecture and collagen fibril organization will be used to evaluate matrix structure. It is important that data from in vitro studies be validated in an animal model and correlated to physiological systems in vivo so that in the long term, relevant experimental results may be extrapolated to a clinical situation in which growth factors may be manipulated to promote healing without scar formation. A fetal lamb model will be used to determine the location and amount of TGFalpha, TGFbeta and PDGFalpha in the surgical site within 48 hours after iatrogenic cleft palate repair at 70 days gestation (minimal scar), 100 days gestation (moderate scar), and 133 days gestation (significant scar). Based on data from in vitro studies, selected components of the ECM will be characterized and measured. Information from these studies will provide the basis for future studies in vivo designed to investigate the cellular mechanisms regulating wound healing in this or other appropriate animal model.
| Thompson, S A; Canady, J W; Coberly, D M et al. (1999) Effects of TGFbeta2 on collagen synthesis in cultured normal and wounded fetal mouse palates. Cleft Palate Craniofac J 36:425-33 |
