Comparison between rhBMP-2 with a hydroxyapatite/β-tri-calcium phosphate/hydrogel carrier graft and autogenous bone graft in the induced membrane technique using a 3D-printed bioactive glass scaffold for critical-sized bone defects in rabbit femurs

초록

Background: In induced membrane technique (IMT) for critical-sized bone defects (CSBDs), surgeons require alternative graft materials for autogenous bone graft (ABG) considering the limited volume of ABG and donor site morbidity. Recombinant human bone morphogenetic protein-2 (rhBMP-2) shows potential, but the outcomes of rhBMP-2 graft in IMT compared with those of ABG have not been investigated. In addition, there have been concerns that the use of rhBMP-2 in IMT may paradoxically lead to worse outcomes. Therefore, this study aimed to determine the outcomes of rhBMP-2 grafting in a rabbit femur CSBD model compared with those with ABG. CSBDs were made in the femur shaft of rabbits, and IMT was performed. Methods: The rhBMP-2 with hydrogel mixed hydroxyapatite (HA)/B-tri-calcium phosphate (B-TCP) carrier graft and ABG from the iliac crest were performed in the BMP and ABG groups, respectively. Both groups received a 3D-printed bioactive glass scaffold, shaped to match the medullary space of the resected segment, to ensure consistent grafting position and volume in each specimen. We compared radiographic, biomechanical, histological, and immunohistochemical evaluation results between the groups. Results: The BMP group had significantly superior results than the ABG group in terms of radiographic scores at 6 (p = 0.010) and 8 weeks (p = 0.003); bone mineral density (p = 0.018); dynamic stiffness before plate removal at 1, 3, 6, and 9 Hz (p = 0.003, 0.001, < 0.001, and < 0.001 respectively); dynamic stiffness after plate removal at 6 and 9 Hz (p = 0.029 and 0.023); static stiffness after plate removal (p = 0.016); and osteopontin expression (p = 0.022). The two groups showed equivalent the bone union rate; volumetric measurement of regenerated bone; viscoelasticity; dynamic stiffness after plate removal at 1 and 3 Hz; static stiffness before plate removal; ratio of mineralized area; cell counts per area of osteocytes, osteoblasts, and osteoclasts; ratio of mature bone area; and osteocalcin expression. Conclusion: RhBMP-2 with HA/B-TCP/hydrogel carrier grafts showed radiographic, biomechanical, histological, and immunohistochemical outcomes comparable with those of ABG in a rabbit model when IMT was used for managing CSBD.

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