EVALUATION OF DELIVERY SYSTEMS FOR GROWTH FACTORS

IT HAS BEEN ESTABLISHED THAT THE COMBINATION OF PLATELET-DERIVED GROWTH FACTOR (PDGF) AND INSULIN GROWTH FACTOR-I (IGF-I) STIMULATES PERIODONTAL REGENERATION IN BEAGLE DOGS WITH NATURALLY OCCURRING PERIODONTAL DISEASE. THIS PROJECT WILL INVESTIGATE MORE EFFECTIVE METHODS OF DELIVERY OF THE PDGF/IGF-1 COMBINATION. DURING PHASE I, IN VITRO AND IN VIVO STUDIES OF FOUR DELIVERY METHODS ARE PLANNED: 3 PERCENT METHYLCELLULOSE GEL POLY (LACTIC ACID) POLYMER, BETA TRICALCIUM PHOSPHATE, AND DEMINERALIZED FREEZE-DRIED BONE ALLOGRAFT. IN VITRO STUDIES WILL INCLUDE INVESTIGATIONS OF THE KINETICS OF ADSORPTION AND RELEASE OF (125)I-PDGF AND (125)I-IGF-1 FROM THE FOUR DELIVERY MODALITIES. IN VIVO STUDIES WILL ALSO BE PERFORMED USING BEAGLE DOGS WITH NATURALLY OCCURRING PERIODONTAL DISEASE. AT THE TIME OF SURGERY, THE TREATMENT SITES WILL RECEIVE PDGF AND IGF-1 DELIVERED BY ONE OF THE FOUR METHODS. CONTROL SITES WILL RECEIVE THE DELIVERY VEHICLE ALONE. PRIOR TO AND AFTER SURGERY, THE UPTAKE OF A BONE-SEEKING RADIOPHARMACEUTICAL (99M-TECHNESIUM MDP) WILL BE MEASURED AND STANDARDIZED RADIOGRAPHS TAKEN. BLOCK BIOPSIES OF THE TEETH AND JAWS WILL BE EXAMINED HISTOLOGICALLY. ANALYSIS OF THESE DATA WILL REVEAL THE ABILITY OF PDGF/IGF-1 DELIVERED BY THE FOUR CARRIERS TO INDUCE PERIODONTAL REGENERATION. HUMAN STUDIES USING PDGF/IGF-1 DELIVERED IN THE OPTIMUM CARRIER ARE THEN ANTICIPATED.