Biologics Development and Carrier Innovation
Most bone graft substitutes currently used in surgery can be broadly categorized into calcium and demineralized bone matrix-based technologies that were developed several decades ago. We have investigated the safety and efficacy of a novel hypercrosslinked carbohydrate polymer (HCCP) for the repair of a critical sized bone defect and lumbar interbody fusion. We also explored the possibility of utilizing HCCP as a carrier for various biologics. For lumbar interbody fusion, we custom-designed HCCP to fit into an interbody cage, implanted into the disc space at L4–5 in sheep (N = 18), and compared it with autologous bone. Animals were monitored by computed tomography (CT), and the implant site was harvested 5 months after implantation. For the repair of a critical-sized bone defect, we implanted HCCP granules (N = 5) into a defect (7 mm × 10 mm) created in the femoral condyle of rabbit and compared them with autologous bone (N = 5) and poly (lactide-co-glycolide) (PLGA)-based substitutes (N = 5). We evaluated with CTs and, at 4 months, histology. At 5 months after implantation, complete spinal fusion was observed in sheep implanted with HCCP at a level comparable with autologous bone, as determined by CT (Figure 1, top) and histologic findings. When implanted in the lateral femoral condyle of rabbits with a critical-sized bone defect, HCCP supported efficient bone formation similarly to autologous bone and the PLGA-based predicate device (Figure 1, bottom). HCCP has been shown to be biocompatible with no pyrogenicity, immunogenicity, cellular toxicity, genotoxicity, or carcinogenicity in in vivo and in vitro studies. We also investigated the ability of HCCP to carry growth factors and cells. HCCP was incubated with bone morphogenetic protein 2 (BMP-2) at 1 μg/mL or with bone marrow mononuclear cells (BM MNCs) at 1 × 107 cells/mL. HCCP was washed and incubated in fresh phosphate-buffered saline for 3 days. BMP-2 and BM MNC released from HCCP were measured by ELISA or by cell counts. Approximately 97% of BMP-2 and BM MNC was retained in HCCP over 3 days. Results indicate that HCCP can (A) be used to promote lumbar interbody fusion; (B) bridge and fill a critical-sized defect similarly to autologous bone; and (C) carry BMP-2 and BM MNC effectively without significant loss of biologics due to leakage.