Proving Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

Background: Large bone defects remain a major clinical challenge for orthopaedic surgeons. Tissue engineered bone grafts have garnered increased attention as a solution to this problem. One ideal property of any bone graft is osteoinductivity or the ability to stimulate progenitor celldifferentiation into a bone forming lineage.Questions: Is the osteoinductive potential of a porcine bone xenograft maintained in vitro after undergoing a novel decellularization and oxidation process? Are porcine bone scaffolds osteoinductive in an in vivo animal model?Methods: In Vitro- C2C12 pre-osteoblasts were seeded on the scaffold or a commercial grade demineralized bone matrix (DBM) to study osteogenic differentiation and compare osteoinductive potential. MC3T3-E1 pre-osteoblasts were seeded on the scaffold and compared to a control monolayer to identify early markers of osteogenic differentiation. In Vivo- MC3T3-E1-seeded scaffolds were implanted subcutaneously in mice and assessed for markers of early osteogenic differentiation, new bone formation (micro-computed tomography and histological assessment), and vascular infiltration (histology).Results: Osteoinductive potential was demonstrated in in vitro experiments by similar osteogenic marker expression compared to DBM and significantly greater expression than a control monolayer. Osteoinductivity was confirmed with in vivo experiments showing both new bone formation and vascular infiltration.Conclusion: Porcine bone maintains osteoinductive properties after decellularization and oxidation.Clinical Relevance: This construct could potentially serve as a bone graft substitute maintaining the osteoinductive potential of native bone. The unrestricted supply and controlled donor biology may satisfy a large clinical need for orthopaedic cases requiring bone grafting.