Proving Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

Bracey, D. N.; Jinnah, A. H.; Whitlock, P.; Hutchinson, I.; Seyler, T.; Willey, J. S.; Danelson, K.; Smith, T. L.; Emory, C. L.; Kerr, B. A.

doi:10.1101/419101

bioRxiv · 10.1101/419101

Proving Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

Bracey, D. N.·Jinnah, A. H.·Whitlock, P.·Hutchinson, I.·Seyler, T.·Willey, J. S.·Danelson, K.·Smith, T. L.·Emory, C. L.·Kerr, B. A.

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Abstract

BackgroundLarge 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 cell differentiation into a bone forming lineage.\n\nQuestionsO_LIIs the osteoinductive potential of a porcine bone xenograft maintained in vitro after undergoing a novel decellularization and oxidation process?\nC_LIO_LIAre porcine bone scaffolds osteoinductive in an in vivo animal model?\nC_LI\n\nMethodsO_LIIn 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.\nC_LIO_LIIn 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).\nC_LI\n\nResultsOsteoinductive potential was demonstrated in in vitro experiments by similar osteogenic marker expression compared to DBM and significantly greater expression than a control monolayer.\n\nOsteoinductivity was confirmed with in vivo experiments showing both new bone formation and vascular infiltration.\n\nConclusionPorcine bone maintains osteoinductive properties after decellularization and oxidation.\n\nClinical RelevanceThis 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.

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Bracey, D. N., Jinnah, A. H., Whitlock, P., Hutchinson, I., Seyler, T., Willey, J. S., Danelson, K., Smith, T. L., Emory, C. L., Kerr, B. A.. 2018-09-17. Proving Osteoinductive Potential of a Decellularized Xenograft Bone Substitute. https://doi.org/10.1101/419101

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