Research training under the auspices of Dr. Samuel Lynch at the Institute of Microbiology and the Harvard School of Medicine has provided an opportunity for through training in molecular and cellular biology as it relates to polypeptide growth factors. Polypeptide growth factors are a class of biologic mediators which promote the profileration, migration, and matrix synthesis of nearly all cells of mesenchymal origins. Polypeptide growth factors have been found in large quantities in bone matrix (In levels up to 20 times higher than that of the circulation). The role of growth factors in bone formation is not well understood, however it is hypothesized that growth factors are produced by osteoblasts, sequester in bone matrix and can be released by and act on bone cells in an autocrine or paracrine manner. Until recently, in vitro cell culture methods have had limitations in allowing the evaluation of the events involved in bone formation. The bovine bone cell culture system (BBCC) appears to more closely resemble the temporal relationship of bone formation in vivo than other current models. Mineralization in this system commences as small nodules that are quickly transformed into trabeculae, which in turn fuse as bone formation continues, finally forming solid sheets of mineralized matrix in 20 days. Various techniques in cellular and molecular biology are being utilized to explore the role of endogenous growth factors during bone formation in this system. Preliminary results have demonstrated the release of Platelet- derived growth factor (PDGF)-like mitogens from the mineralizing osteoblasts by the use of immunoneutralization in situ hybridization and correlating PDGF-expression with mineral deposition, osteoblast differentiated phenotype and collagen expression. Future work with this model may aid in the understanding of the complex mechanisms of ossification and provide a framework by which one can rationally design growth factor related therapy in promoting bone growth following trauma (e.g. fracture repair) or disease (e.g. periodontal disease). The second tier of training thus far has involved the use of polypeptide growth factors in vivo models of osteogenesis and periodontal wound healing. In these studies the topical application of growth factors, PDGF, Insulin-like growth factor (IGF-I), and the combination of both factors was assessed in promoting periodontal regeneration. These studies utilized cyamalogous monkeys with ligature-induced periodontitis. The growth factor and growth factor combinations treatments were divided into 3 groups in a split-mouth design with the contralateral guadrants serving as controls. The results evaluating the effects of the growth at 4 and 12 weeks post-application demonstrated enhanced periodontal regeneration with the PDGF/IGF-I growth factor combination. Results were attained by histomorphometric analysis of tissue sections showing increases in new bone height and area, as well as new connective tissue attachment (i.e. with new cementum and periodontal ligament). The results from this study further substantiate the use of growth factors in promoting osteogenesis and periodontal wound healing. Key Words: growth factors, wound healing, bone formation
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