Delivery of Recombinant Human Bone Morphogenetic Protein-2 Using a Compression-Resistant Matrix in Posterolateral Spine Fusion in the Rabbit and in the Non-Human Primate

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Abstract
A rabbit and rhesus monkey model of posterolateral intertransverse process spine arthrodesis was used. To test two new soft tissue compression resistant ceramic/collagen sponge carriers for recombinant human bone morphogenetic protein-2. After determining that a plain collagen sponge was too compressible for large animals in a posterolateral fusion application, the authors demonstrated good bone induction using biphasic ceramic phosphate granules (60% hydroxyapatite/40% tricalcium phosphate) as the carrier matrix for recombinant human bone morphogenetic protein 2 in rhesus monkeys. A limitation of 60:40 biphasic ceramic phosphate was its slow resorption time caused by the high hydroxyapatite content, making radiographic detection of new bone formation very difficult. Adult New Zealand white rabbits (n = 14) underwent posterolateral spine arthrodesis at L5–L6 using 5:95 biphasic ceramic phosphate (5% hydroxyapatite/95% tricalcium phosphate) impregnated Type I collagen sponges (17 × 35 × 2.5 mm, two per side) loaded with 0.86 mg recombinant human bone morphogenetic protein 2. Additional rabbits (n = 14) received 60:40 hydroxyapatite-tricalcium phosphate granules as the carrier for bone morphogenetic protein 2. Adult rhesus monkeys (n = 6) underwent posterolateral arthrodesis at L4–L5 with ceramic/collagen sponge carrier loaded with 9 mg recombinant human bone morphogenetic protein 2 per side. Two monkeys received ceramic/collagen sponges containing 15:85 biphasic ceramic phosphate (15% hydroxyapatite/85% tricalcium phosphate) with two pieces per side; two received sponges containing 5:95 biphasic ceramic phosphate with two pieces per side, and two received sponges containing 5:95 biphasic ceramic phosphate with four pieces per side. The rabbits were killed after 5 weeks and the monkeys after 24 weeks; the spines were evaluated by manual palpation, radiographs, tensile mechanical testing (rabbits only), and histology. The recombinant human bone morphogenetic protein 2 delivered in the 5:95 biphasic ceramic phosphate/collagen sponge achieved fusion in 100% of rabbits and had improved handling properties compared with the biphasic ceramic phosphate granules. Biomechanical results with 5:95 biphasic ceramic phosphate/collagen carrier were comparable to those obtained with the 60:40 biphasic ceramic phosphate granules and superior to those of autogenous bone graft (P The new compression-resistant biphasic ceramic phosphate/collagen sponge matrices were biologically compatible with recombinant human bone morphogenetic protein 2 bone formation, resulted in biomechanically stiffer fusion masses than autograft, better space maintenance than plain collagen sponges, and improved handling and radiographic resorption properties over the ceramic carriers previously tested.