Potential of porous poly-D,L-lactide-co-glycolide particles as a carrier for recombinant human bone morphogenetic protein-2 during osteoinduction in vivo

Several different biodegradable bone graft materials are in clinical or pre clinical use for the repair of bone defects in orthopedics, maxillofacial s urgery, and periodontics. This study tested the hypothesis that poly-D,L-la ctide-co-glycolide copolymer (PLG) can be used as an effective carrier of r ecombinant human bone morphogenetic protein-2 (rhBMP-2) and that the compos ite has osteoinductive ability. Porous PLG rods were shredded to a particle size ranging from 250 to 850 mu m Active and inactive demineralized freeze -dried bone allografts (DFDBA) with a comparable particle size were used as positive and negative controls, respectively. PLG particles were treated w ith vehicle or with 5 or 20 mu g rhBMP-2. DFDBA and PLG particles were plac ed in gelatin capsules, mixed with vehicle or rhBMP-2, and implanted at int ramuscular sites in male Nu/Nu (nude) mice. Each mouse underwent bilateral implantation with implants of the same formulation, resulting in five group s of four mice per group: active DFDBA, inactive DFDBA, PLG, PLG + 5 mu g r hBMP-2, and PLG + 20 mu g rhBMP-2. After 56 days, the implants were recover ed and processed for histology. Bone induction was assessed by use of a sem iquantitative scoring system based on the amount of new bone formed in repr esentative histological sections. Histomorphometry was also used to measure the area of new bone formed and the area of residual implant material. The results showed that active DFDBA induced the formation of ossicles contain ing new bone with bone marrowlike tissue, whereas inactive DFDBA or PLG par ticles alone did not induce new bone. The addition of rhBMP-2 to PLG partic les resulted in new bone formation that had a greater bone induction score than active DFDBA. Moreover, the histomorphometric analysis showed that the addition of rhBMP-2 to PLG particles induced the formation of a greater ar ea of new bone and bone marrowlike tissue than active DFDBA. The resorption of the PLG particles was markedly increased with the addition of rhBMP-2, suggesting that rhBMP-2 may attract and regulate resorptive cells at the im plantation site. The results of the present study indicate that PLG copolym ers are good carriers for BMP and promote the induction of new bone formati on. Further, the PLG copolymers with rhBMP-2 had a greater effect in induci ng new bone formation and resorbing the implanted material than active DFDB A alone. (C) 1999 John Wiley & Sons, Inc.