Experimental Spinal Fusion With Recombinant Human Bone Morphogenetic Protein-2 Delivered by a Synthetic Polymer and β-Tricalcium Phosphate in a Rabbit Model

In Brief Study Design. An experimental animal study to achieve posterolateral intertransverse process spine fusion with recombinant bone morphogenetic protein in combination with a new delivery system. Objective. To evaluate the efficacy of a new synthetic biodegradable bone-inducing material containing recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone-graft substitute for posterolateral intertransverse process fusion in a rabbit model. Summary of Background Data. rhBMP-2, a powerful bone-inducing cytokine, has been used as a bone graft substitute in combination with animal-derived collagen to achieve spinal fusion in animal models. However, the minimum dose of rhBMP-2 required to obtain solid posterolateral intertransverse process fusion was high on the basis of previous reports (>100 μg in rabbit models). To improve the efficacy, performance of rhBMP-2, and the safety of the delivery system for this protein, a more sophisticated system is required. Methods. To fabricate one implant for one-side L4–L5 intertransverse process fusion, β-tricalcium phosphate (β-TCP) powder (300 μg), a polymer gel (PLA-DX-PEG block copolymer; 300 μg) and rhBMP-2 (7.5, 15, or 30 μg) were mixed and manually shaped to resemble a rod. Through a posterolateral approach, two implants were placed on both sides (1 per side) by surgery so as to bridge the transverse processes of adult New Zealand white rabbits (n = 27). In control animals, implants without rhBMP or autogenous cortico-cancellous bone chips from the iliaccrest were placed in a similar location. The lumbar vertebrae were recovered 6 weeks after surgery. The posterolateral fusion was examined by manual palpation, radiography, biomechanical testing, and histology. Results. Rabbits that received 15 or 30 μg of rhBMP-2 showed consistent fusion. However, solid fusion was seen in 2 of 5 rabbits with autografting and rabbits that received 7.5 μg of rhBMP-2. Fusion was not observed in the rabbits that did not receive rhBMP-2. Conclusions. Consistent spinal fusion was obtained by implanting a biodegradable bone-inducing implant composed of β-TCP, PLA-DX-PEG, and rhBMP-2 within a period of 6 weeks. The rhBMP-2 doses required for the spinal fusion were significantly lower than those reported previously. The efficacy of the β-tricalcium phosphate/PLA-DX-PEG composite that contained low doses of recombinant human bone morphogenetic protein-2 was evaluated in a rabbit spine fusion model. All experimental animals that received 15 μg of recombinant human bone morphogenetic protein-2 on each side, which is a significantly lower efficacious dose than previously reported, achieved solid fusion within 6 weeks. This study demonstrated the potential of the new material as an autogenous bone graft substitute.