Bone Regeneration by Low-dose Recombinant Human Bone Morphogenetic Protein-2 Carried on Octacalcium Phosphate Collagen Composite

Abstract

Bone morphogenetic protein-2 (BMP-2) has diverse functions and is especially important in bone and cartilage development. Recombinant human BMP-2 (rhBMP-2) is an osteoinductive growth factor that has been clinically applied as a bone graft substitute. However, high-dose rhBMP-2 can cause complications such as induction of significant swelling that can endanger the patient's life. Atelocollagen sponge (ACS) is the commercially provided standard carrier of rhBMP-2 in clinical applications. However, a large concentration of rhBMP-2 is required to be clinically effective with ACS as the carrier. Octacalcium phosphate/collagen (OCP/Col) has been shown to be an excellent bone substitute compared with other bone substitute materials such as hydroxyapatite or β-tricalcium phosphate due to its biological properties. In this study, we evaluated the use of OCP/Col as a carrier to minimize the effective dose of rhBMP-2. ACS or OCP/Col discs impregnated with different rhBMP-2 concentrations were implanted in mice calvarial bone defects. Morphological analysis with micro-CT both at 4 and 6 weeks post-implantation showed homogenous hard tissue formation in the defects of the OCP/Col group at all rhBMP-2 concentrations tested (0, 0.25, 0.50, or 1.00 μg). In contrast, ACS alone or with 0.25 μg of rhBMP-2 showed almost no bone formation. However, bone mineral density in all groups of ACS and OCP/Col was not dependent on rhB-MP-2 concentration. Histological evaluation indicated that bone formation progressed depending on rhBMP-2 concentration in the defects of both the ACS and OCP/Col groups, although the newly formed bone area was significantly higher in the OCP/Col group than in the ACS group. These results indicate that OCP/Col could be an effective carrier of rhBMP-2, minimizing the application dose of rhBMP-2 in clinical settings and avoiding the complications caused by high-dose rhB-MP-2.

Human Fresh Fibrin Membrane with Bone Morphogenetic Protein-2 (BMP-2) Induces Bone Formation in the Subcutaneous Tissues of Nude Mice

“…Since the discovery of bone morphogenetic proteins (BMPs) [ 13 , 14 ], the delivering carriers of BMPs have been explored. Recombinant human BMP-2 (rhBMP-2), a potent exogenous osteo-inductive cytokine, requires a delivery system that creates optimal conditions for cellular and vascular growth and cellular attachment, as well as a matrix for adsorption [ 15 , 16 , 17 , 18 , 19 ]. Collagenous materials or ceramics combined with rhBMP-2 have been commercially available for clinical use [ 20 , 21 ].…”

Can a low dosage of recombinant human bone morphogenetic protein-2 loaded on collagen sponge induce ectopic bone?

“…In the present study, osteogenesis was evaluated subcutaneously, but in clinical practice, rhBMP-2 can be used directly on bone tissues, where the bone always forms. Therefore, even at doses lower than one-tenth of the recommended rhBMP-2 dose, bone may form in the bone defects 34) . When considering the side effects of rhBMP-2, use of lower concentrations is safer and presents a lower cost burden.…”

Tissue engineering applications of recombinant human collagen: a review of recent progress

“…This is achieved through manipulation of collagen crosslinking, mineral content, and the incorporation of bioactive motifs, enabling a controlled degradation rate that synchronizes with new bone deposition ( Bien et al, 2020 ). Moreover, rhCOL scaffolds surpass the limitations of traditional bone graft materials by supporting cellular growth and providing precise control over structural and functional properties ( Muhonen et al, 2017 ; Bien et al, 2020 ). Ongoing research endeavors aim to optimize integration and healing outcomes as rhCOL transitions from laboratory research to clinical implementation for bone engineering applications.…”