Bovine bone particulates containing bone anabolic factors as a potential xenogenic bone graft substitute
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(2019) 14:60
RESEARCH ARTICLE
Open Access
Bovine bone particulates containing bone anabolic factors as a potential xenogenic bone graft substitute David S. Musson1* , Ryan Gao1, Maureen Watson1, Jian-Ming Lin1, Young-Eun Park1, Donna Tuari1, Karen E. Callon1, Mark Zhu1,2, Nicola Dalbeth1, Dorit Naot1, Jacob T. Munro2,3 and Jillian Cornish1
Abstract Background: Alternative grafts are needed to improve the healing of bone non-union. Here, we assessed a bovine bone product which retains the inorganic and organic components of bone, as an alternative bone graft. Methods: Bovine bone matrix proteins (BBMPs) were isolated from bovine bone particulates (BBPs) and tested in vitro. Primary rat osteoblast viability, differentiation, and mineralisation were assessed with alamarBlue®, real-time PCR, and von Kossa staining assays, respectively. Osteoclast formation was assessed in primary murine bone marrow cultures with TRAP staining. Human osteoblast growth and differentiation in the presence of BBPs was evaluated in 3D collagen gels in vitro using alamarBlue® and real-time PCR, respectively. The efficacy of BBPs as an alternative bone graft was tested in a rat critical-size calvarial defect model, with histology scored at 4 and 12 weeks post-surgery. Results: In vitro, the highest concentration of BBMPs increased mineral deposition five-fold compared to the untreated control group (P < 0.05); enhanced the expression of key osteoblast genes encoding for RUNX2, alkaline phosphatase, and osteocalcin (P < 0.05); and decreased osteoclast formation three-fold, compared to the untreated control group (P < 0.05). However, the BBPs had no effect on primary human osteoblasts in vitro, and in vivo, no difference was found in healing between the BBP-treated group and the untreated control group. Conclusions: Overall, despite the positive effects of the BBMPs on the cells of the bone, the bovine bone product as a whole did not enhance bone healing. Finding a way to harness the positive effect of these BBMPs would provide a clear benefit for healing bone non-union. Keywords: Xenogenic bone graft, Demineralised bone, Bovine bone, Osteoblast, Osteoclast
Background Despite advances in modern fracture management, up to 5% of all fractures and 20% of high energy fractures fail to adequately heal, leading to non-union [1]. Furthermore, common elective orthopaedic procedures, such as spinal fusions, are associated with high non-union rates (< 35%) [2–5]. Currently, autologous bone is the gold standard graft material for encouraging bony union in elective spinal, oncological, and maxillofacial procedures. * Correspondence: [email protected] 1 Department of Medicine, University of Auckland, Auckland 1142, New Zealand Full list of author information is available at the end of the article
Whilst effective, autologous bone grafting is limited by the finite amount of bone that can be safely harvested, the need for a second surgical site, and significant donor site morbidity [6–9]. In order to circumvent the shortcomings of autologous bone
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