The major goal of clinical periodontal therapy is the regeneration of the periodontal ligament attachment to the surface dentin of the tooth. However, current surgical therapy results in the loss of a substantial portion of the attachment apparatus. No therapy results in chronic inflammatory periodontitis with eventual tooth loss. Recent in vitro work in this laboratory indicates that polypeptide growth factors and appropriate extracellular matrix components are capable of stimulating the chemotaxis and proliferation of cells that could participate in the healing of the periodontal wound in vivo. In vitro this combination of factors stimulates the attachment and migration of specific cell types to biochemically modified dentin surfaces. The failure of these cells to attach and migrate to the prepared dentin surfaces in vivo suggests that there are either inhibitory factors or a lack of stimulatory factors. Macrophages, which partially control the rate, extent and nature of normal wound healing, can promote both inflammation and repair. While in the inflammatory phase, macrophages secrete factors that inhibit specific cell chemotaxis and mitogenesis. While in the repair phase, macrophages secrete factors that promote migration and proliferation. Biochemical and molecular biological techniques will be utilized to characterize these transition phases of human macrophages and their effect on human gingival epithelial and fibroblast cells, human periodontal ligament cells and human endothelial cells. Pharmacologic manipulation of these macrophage induced effects will also be investigated. The hypothesis of this proposal is that macrophages, in the special environment of the periodontal wound, fail to progress from an inflammatory phase to a phase that promotes wound repair. We hypothesize that it is possible to induce a macrophage repair phase phenotype.
