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Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.

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Autologous bone graft substitute (ABGS) containing rhBMP6 in autologous blood coagulum (Osteogrow) is a novel therapeutic solution for bone regeneration. This study is aimed to investigate the long-term outcome of ABGS with synthetic ceramics (Osteogrow-C) in rabbit posterolateral spinal fusion (PLF) model. Osteogrow-C implants were implanted bilaterally between rabbit lumbar transverse processes. We compared the outcome following implantation of ABGS with ceramic particles of different chemical composition (TCP and biphasic ceramics containing both TCP and HA) and size (500–1700 µm and 74–420 µm). Outcome was analyzed after 14 and 27 weeks by microCT, histology, and biomechanical analyses. Successful bilateral spinal fusion was observed in all animals at the end of observation period. Chemical composition of ceramic particles has impact on the PLF outcome via resorption of TCP ceramics, while ceramics containing HA were only partially resorbed. Moreover, persistence of ceramic particles subsequently resulted with an increased bone volume in implants with small particles containing high proportion of HA. ABGS (rhBMP6/ABC) with various synthetic ceramic particles promoted spinal fusion in rabbits. This is the first presentation of BMP-mediated ectopic bone formation in rabbit PLF model with radiological, histological, and biomechanical features over a time course of up to 27 weeks.

Autologous bone graft substitute (ABGS) containing rhBMP6 in autologous blood coagulum (ABC) with synthetic ceramics is a novel therapeutic solution for bone repair. The aim of this study was to investigate whether the application of Zoledronate (ZOL) with ABGS might enhance the properties of newly formed bone. The effect of ZOL on bone induction was tested in a rat subcutaneous implant model. ZOL bound to synthetic ceramics was added into ABGS implants, and the quantity, quality, and longevity of the induced bone were assessed by micro-CT, histomorphometry, and histology over a period of 365 days. Local use of ZOL in the ABGS implants with ceramics had no influence on the bone volume (BV) on day 14 but subsequently significantly increased BV on days 35, 50, 105, 140, and 365 compared to the control implants. Locally applied ZOL had a similar effect in all of the applied doses (2–20 µg), while its systemic use on stimulating the BV of newly induced bone by ABGS depended on the time of application. BV was increased when ZOL was applied systemically on day 14 but had no effect when applied on day 35. The administration of ZOL bound to ceramics in ABGS increased and maintained the BV over a period of one year, offering a novel bone tissue engineering strategy for treating bone defects and spinal fusions.

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Background Management of large segmental defects is one of the most challenging issues in bone repair biology. Autologous bone graft substitute (ABGS) containing rhBMP6 within autologous blood coagulum (ABC) with synthetic ceramics is a novel biocompatible therapeutic solution for bone regeneration. Case presentation A 2-year old dog was brought to the veterinary clinics due to pain and bleeding from the right front leg after being unintendedly hit by a gunshot. Radiological examination revealed a large, 3 cm long multisegmental defect of the humerus on the right front leg with a loss of anatomical structure in the distal portion of the bone. The defect was treated surgically and an external fixator was inserted to ensure immobilization. Complete lack of bone formation 3 months following surgery required a full reconstruction of the defect site with a novel ABGS (rhBMP6 in ABC with ceramic particles) to avoid front leg amputation. The healing was then followed for the next 16 months. The callus formation was observed on x-ray images 2 months following ABGS implantation. The bone segments progressively fused together leading to the defect rebridgment allowing removal of the external fixator by 4 months after the reconstruction surgery. At the end of the observation period, the function of the leg was almost fully restored while analyses of the humeral CT sections revealed restoration and cortices rebridgment with a renewal of uniform medullary canal including structural reconstruction of the distal humerus. Conclusion This large humeral gunshot segmental defect of the front leg in a dog was saved from amputation via inducing bone regeneration using a novel ABGS osteoinductive device containing BMP6 in ABC.