Shuji Nosho1,2,3, Mitsuaki Ono2,3, Taishi Komori1, Akihiro Mikai1,2,3, Ikue Tosa1, Kei Ishibashi1,2,3, Yukie Tanaka1,2,3, Aya Kimura-Ono3,4, Emilio S Hara5, Toshitaka Oohashi2, Takuo Kuboki1,3. 1. Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 2. Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 3. Department of Oral Rehabilitation and Implantology, Okayama University Hospital, Okayama, Japan. 4. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. 5. Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Abstract
PURPOSE: Bone morphogenetic protein (BMP)-2 is a potent growth factor that is widely used in the orthopedic and dental fields for bone regeneration. However, recombinant human BMP-2 (rhBMP-2) products have not been legally approved in Japan. Recently, our research group succeeded in producing GMP-grade rhBMP-2 using the E. coli system (E-rhBMP-2) at the industrial level and developed E-rhBMP-2 adsorbed onto β-TCP (E-rhBMP-2/β-TCP) as an alternative material to autogenous bone grafts. Previous studies on the toxicity, pharmacokinetics, and optimal doses of E-rhBMP-2 have confirmed its safety and efficiency. However, comparative studies with standard treatment therapies are still necessary before clinical application in humans. Therefore, in this preclinical study, we compared the bone regeneration ability of E-rhBMP-2/β-TCP and autogenous bone grafts in a canine guided-bone regeneration model. METHODS: Following extraction of the maxillary third premolar, box-type bone defects (10 mmL × 4 mmW × 9 mmH) were created in the extraction socket area and transplanted with E-rhBMP-2/β-TCP or autogenous bone graft in a canine. After 8 weeks, micro-CT and histological analyses were performed. RESULTS: Transplantation of both E-rhBMP-2/β-TCP and autogenous bone graft significantly promoted bone formation compared to the non-transplantation control group. The bone formation ability of E-rhBMP-2/β-TCP was equal to that of the autogenous bone graft. Histological analysis showed that excessive infiltration of inflammatory cells and residual β-TCP particles mostly were not observed in the E-rhBMP-2/β-TCP transplantation group. CONCLUSION: This preclinical study demonstrated that E-rhBMP-2/β-TCP and autogenous bone have equal potential to promote bone regeneration.
PURPOSE: Bone morphogenetic protein (BMP)-2 is a potent growth factor that is widely used in the orthopedic and dental fields for bone regeneration. However, recombinant human BMP-2 (rhBMP-2) products have not been legally approved in Japan. Recently, our research group succeeded in producing GMP-grade rhBMP-2 using the E. coli system (E-rhBMP-2) at the industrial level and developed E-rhBMP-2 adsorbed onto β-TCP (E-rhBMP-2/β-TCP) as an alternative material to autogenous bone grafts. Previous studies on the toxicity, pharmacokinetics, and optimal doses of E-rhBMP-2 have confirmed its safety and efficiency. However, comparative studies with standard treatment therapies are still necessary before clinical application in humans. Therefore, in this preclinical study, we compared the bone regeneration ability of E-rhBMP-2/β-TCP and autogenous bone grafts in a canine guided-bone regeneration model. METHODS: Following extraction of the maxillary third premolar, box-type bone defects (10 mmL × 4 mmW × 9 mmH) were created in the extraction socket area and transplanted with E-rhBMP-2/β-TCP or autogenous bone graft in a canine. After 8 weeks, micro-CT and histological analyses were performed. RESULTS: Transplantation of both E-rhBMP-2/β-TCP and autogenous bone graft significantly promoted bone formation compared to the non-transplantation control group. The bone formation ability of E-rhBMP-2/β-TCP was equal to that of the autogenous bone graft. Histological analysis showed that excessive infiltration of inflammatory cells and residual β-TCP particles mostly were not observed in the E-rhBMP-2/β-TCP transplantation group. CONCLUSION: This preclinical study demonstrated that E-rhBMP-2/β-TCP and autogenous bone have equal potential to promote bone regeneration.
Entities:
Keywords:
BMP-2; Bone formation; Preclinical study