Controlled Delivery of Low-Dose Bone Morphogenetic Protein-2 Using Heparin-Conjugated Fibrin in the Posterolateral Lumbar Fusion of Rabbits

The heparin-conjugated fibrin (HCF) system has been developed to deliver bone morphogenetic proteins (BMPs) for a long-term period and thus enhance bone regeneration. In the present study, we tested the effectiveness of the delivery system for spinal fusion with a very low dose of BMP-2. A total of 15 rabbits underwent posterolateral lumbar spine, divided into three groups. The control group received only collagen sponges without BMP-2, another group (BMP-only group) received collagen sponges loaded with BMP-2 (10μg each side), and the last group (BMP/HCF group) received collagen sponges filled with HCF loaded with BMP-2 (10μg each side). All animals were euthanized 8 weeks after surgery, and the fusion was assessed by radiographs, manual palpation, computed tomography scan, and mechanical testing. No case in the BMP/HCF group or in the control group achieved solid fusion, while all cases in BMP-only group showed evidence of solid fusion. BMP/HCF group had significantly lower fusion rate and tensile strength than BMP-only group at the dose of 10μg of BMP-2. The HCF long-term delivery system with the low dose of BMP-2 (10μg) is ineffective for the induction of lumbar posterolateral fusion in the rabbits.