TIME COURSE OF ECTOPIC BONE FORMATION IN RATS INDUCED BY rhBMP6 WITHIN AUTOLOGOUS BLOOD COAGULUM WITH CALCIUM PHOSPHATE CERAMIC PARTICLES

Jun 29, 2022, 11:50 AM
10m
Room: S4 B

Room: S4 B

Speaker

Stokovic, Nikola (Laboratory for Mineralized Tissues, School of Medicine University of Zagreb )

Description

"Introduction: Osteoinductive bone morphogenetic proteins (BMPs) possess the ability to induce bone formation and therefore have been the basis of osteoinductive devices designed for bone regeneration. Osteogrow C is a novel autologous bone graft substitute comprised of recombinant human Bone Morphogenetic Protein 6 (rhBMP6) within autologous blood coagulum (ABC) with synthetic calcium phosphate (CaP) ceramic particles. CaP particles serve as a compression resistant matrix and are available in a broad range of shapes and sizes. The aim of this study was to investigate the time course of ectopic bone formation in rats following subcutaneous implantation of rhBMP6/ABC with CaP particles in a size range from 2360 to 4000 µm.
Methodology: Osteogrow C osteoinductive device was prepared as follow: rhBMP6 (20 µg per implant) was added to autologous blood (500 µL), mixed with synthetic ceramic particles (size range: 2360-4000 µm; chemical composition: TCP/HA 80%/20%; porosity: 86%; average pore size: 246 µm) and left to coagulate at room temperature. Subcutaneous pockets were created in the axillary region of Sprague Dawley rats (male, 6-8 weeks, 250-300 g), and following blood coagulation, osteoinductive devices were implanted in pockets. Animals were killed on days 7, 14, 21, and 35 following implantation. Extracted implants were analyzed on histological and microCT sections to investigate the time course of ectopic bone formation.
Results: MicroCT analyses revealed that Osteogrow C implants induced extensive bone formation two weeks after implantation at rat ectopic site. Histological analyses have shown that seven days after implantation large areas of endochondral ossification were present only at the peripheral parts of the implants while on day 14 endochondrally formed bone was present throughout the implant between ceramic particles. On day 21 following implantation BMP-induced osteogenesis has reached its final stage and ectopic bone was present at the ceramic surfaces, in the pores, and between the particles. At the end of the observation period (day 35) the structural properties of newly formed bone were similar as on day 21, however, the thickness of trabeculae between the particles was decreased while the number of adipocytes was increased and they became the predominant cell population in the bone marrow.
Conclusions: In the present study we have elucidated dynamics of ectopic bone formation following implantation of rhBMP6 in ABC with ceramics (Osteogrow C). Osteogrow C implants with large (2360-4000 µm) ceramic particles induced bone in rat ectopic site proving excellent osteoinductive properties of tested implants. Therefore, Osteogrow C is a promising novel therapeutic solution for bone regeneration."

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