No abstract

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.

Bone Morphogenetic Proteins (BMPs) are growth and differentiation factors within the TGFβ superfamily of proteins. They induce ectopic and orthotopic endochondral bone formation and are involved in the regulation of cell proliferation, differentiation, apoptosis and mesenchymal-epithelial interactions in critical morphogenetic processes of tissues beyond bone. BMP2 and BMP7 osteogenic devices have been approved for enhancing healing in patients with long bone defects and anterior spinal fusion procedures. However, due to a high price and various serious adverse events including heterotopic ossification, retrograde ejaculation and pain their clinical use have been limited. In this review we discuss the BMP discovery, biology and their use in clinical studies with particular reference to the newly developed BMP6 based autologous bone graft substitute (ABGS). A novel ABGS consisting of an autologous bone coagulum (ABC) carrier with dispersed BMP6 to initiate the differentiation of mesenchymal cells into endochondral bone. The ABC met the conditions for an optimal delivery system for BMP6 due to handling simplicity, without an immunogenic and inflammatory response at the implantation site. Addition of allograft or synthetic ceramics to ABGS demonstrated in animal models significantly increased volume

who got an insight into the latest achievements in basic, translational, and clinical research of BMP molecules through 75 lectures categorized into several scienti c sections. is review paper provides the most important novel ndings on the structure, function, and signaling of BMPs, the role of BMPs in patterning and organoids as well as the role of BMP in metabolism. Moreover, we discussed the role of BMPs in various diseases including cancer pathogenesis, pulmonary arterial hypertension, and brodysplasia ossi cans progressiva (FOP). Finally, we provided an overview of the new BMP-based therapies in regenerative medicine that are currently in di erent stages of preclinical and clinical trials.

Treatment of large bone defects and degenerative diseases of the spine is among the most challenging and still unresolved issues in clinical medicine. erefore, substantial e ort has been devoted to the development of novel bone regenerative therapies. Due to their potent osteoinductive properties, Bone Morphogenetic Proteins (BMPs) have been the basis for the development of novel strategies for bone regeneration. e use of animal models is an indispensable part of the preclinical testing of novel therapeutic solutions. e rat subcutaneous assay became the initial screening procedure for the evaluation of promising BMP-based osteoinductive devices for bone regeneration because only osteogenic BMPs can induce new bone at any ectopic rodent site. Moreover, this model is used for research on the mechanisms of ectopic bone formation as well as for the evaluation of the in ammatory response to di erent materials. In this review, we provided an overview of the assay development and previously conducted studies with di erent methods ( ow cytometry, histological and microCT analyses) for the study outcome evaluation. Moreover, we addressed essential issues in the experimental design such as the follow-up period and the sample size. e rat subcutaneous bone induction assay layed the foundation for isolation and identi cation of BMPs followed by testing of new osteogenic devices in higher animal species and humans.