HEALING OF LARGE SEGMENTAL DEFECTS IN RAT FEMURS IS AIDED BY RHBMP-2 IN PLGA MATRIX

Recombinant human bone morphogenetic protein-2 (rhBMP-2) can be used to enhance the repair of congenital or acquired bone pathologies when formulated in the appropriate carrier. Poly [D,L-(lactide-co-glycolide)] (PLGA) has been shown to be an effective carrier of rhBMP-2. We investigated several particle sizes PLGA and several doses of rhBMP-2 in a rat orthotopic model. We also investigated the effects of a fibrinolytic inhibitory agent, epsilon aminocaproic acid (EACA), on the healing response. Our data indicate that higher doses of rhBMP-2 resulted in increased failure torque (408 +/- 70 N-mm or 60% of the intact value) and higher incidence of union (100%). The induced bone in femurs treated with the smaller particle size PLGA achieved the greatest torsional stiffness and strength. The presence of rhBMP-2 was necessary for new bone to form, but the presence of EACA did not change these results; the use of the PLGA carrier appeared to increase bone strength and stiffness. In fact, with higher doses of rhBMP-2 in PLGA, the stiffness of the new bone was equal to that of intact controls (64 +/- 20 N-mm/deg [intact femurs] versus 45 +/- 10 N-mm/degree [medium dose in small PLGA], 61 +/- 17 N-mm/degree [high dose in small PLGA], and 36 +/- 11 N-mm/degree [medium dose in large PLGA]; P > .05). In conclusion, PLGA implanted with rhBMP-2 effectively aided in healing large segmental defects in rat femurs. (C) 1994 John Wiley & Sons, Inc.