Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion.

Abstract

A nonhuman primate lumbar intertransverse process arthrodesis model was used to evaluate modifications to a plain collagen sponge to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2). To evaluate the feasibility of enhancing the delivery of rhBMP-2 with the established collagen sponge carrier by adding biphasic ceramic phosphate (BCP) granules (15% hydroxyapatite, 85% tricalcium phosphate) or allograft chips to provide compression resistance for posterolateral spine arthrodesis. Recombinant human bone morphogenetic protein-2 was successfully delivered with a resorbable collagen sponge in a rabbit intertransverse process fusion model. Success in nonhuman primates required a higher dose (6-9 mg) of rhBMP-2 and a more compression-resistant matrix (ceramic) than plain collagen. The limitation of the ceramic carrier was its radiopacity, which made radiographic detection of new bone formation difficult. Nine adult rhesus monkeys underwent bilateral posterolateral intertransverse process arthrodesis at L4-L5. The animals were divided into three groups (n = 3 each) based on the graft material implanted: 1) autogenous iliac crest bone (5 cm3/side); 2) collagen sponge and 15:85 BCP granules loaded with rhBMP-2 (3 mg/side); and, 3) collagen sponge and allograft chips loaded with rhBMP-2 (3 mg/side). The monkeys were killed 24 weeks after surgery. Inspection, manual palpation, radiography, computed tomographic scans, and histology were used to assess fusion. All six monkeys with rhBMP-2 delivered in the collagen/15:85 BCP carrier and the collagen/allograft chips carrier achieved solid spine fusions, whereas only one of three animals fused with autogenous bone graft. Histologic analysis of the bone induced by rhBMP-2 showed normal trabecular bone and bone marrow elements. The addition of either 15:85 BCP granules or allograft bone chips to the existing resorbable collagen sponge matrix enhanced delivery of rhBMP-2 in the posterolateral spine. The combination matrices were more compression resistant and had improved radiographic resorption properties that permitted easy radiographic visualization of new bone. In addition, a lower dose of rhBMP-2 (3 mg/side) was successful compared with the dose previously used with the plain collagen sponge (6 mg/side).