Healing of large segmental defects in rat femurs is aided by RhBMP‐2 in PLGA matrix

Abstract

Recombinant human bone morphogenetic protein‐ (rhBMP‐) 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‐. We investigated several particle sizes PLGA and several doses of rhBMP‐ 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‐ 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‐ 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‐ 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‐ effectively aided in healing large segmental defects in rat femurs. © 1994 John Wiley & Sons, Inc.