USE OF BONE MORPHOGENETIC PROTEIN-2 IN THE RABBIT ULNAR NONUNION MODEL

The ability of the osteoinductive protein and recombinant human bone m orphogenetic protein-2, combined with polylactic glycolic acid porous microspheres and autologous blood clot to heal a large segmental defec t was tested in a rabbit diaphyseal defect model. Two centimeter nonun iting defects were surgically created in the bilateral ulnae of 50 mal e Neu Zealand white rabbits, Each defect was then implanted with a pas telike polylactic glycolic acid/blood clot combination that was mixed with 5 different concentrations of recombinant human bone morphogeneti c protein-2, The forearms were radiographically assessed oil a biweekl y schedule for 8 weeks. At 8 weeks. all animals were sacrificed and fo rearms radiographed. Radiographs were then scored by 3 independent obs ervers for bone formation and union rates, United limbs were tested in torsion for mechanical strength using a Burstein torsion tester, All nonunited limbs were analyzed histologically as were 2 united limbs fi om each dosage group, Radiographic evaluation revealed that there was a lose dependent response ill healing of the ulnar defect with a high er bone formation rate in the 2 higher dose limbs than in the lower do se limbs. Union was achieved in 100% of the highest dose limbs, wherea s only 50% of the lowest dose limbs achieved bony union, Na defects Im planted with carrier alone achieved union, Biomechanical studies revea led significantly stiffer bone than age matched controls, Histologic a nalysis demonstrated normal bone formation with abundant normal appear ing osteoid. These dose response data further support the role of reco mbinant human bone morphogenetic protein-2 as a potent morphogen in bo ne regeneration.