Regenerative effect of human cell-derived BMP-2 cultured within a collagen bone graft in a rat calvaria defect model

Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive factor; however, current clinical applications using <i>Escherichia coli</i>-derived recombinant human BMP-2 are constrained by structural deficiencies and high-dose requirements, which increases the risk of adverse effects. In this study, we aimed to address these limitations by developing a novel approach leveraging genetically engineered human retinal pigment epithelial cells (ARPE-19) to synthesize human cell-derived BMP-2 (hBMP-2) within a collagen-based bone graft matrix. ARPE-19 cells were transduced using a lentiviral vector encoding BMP-2 and subsequently cultured in a porcine-collagen mixed graft material. The efficacy of this hBMP-2-enriched graft was evaluated in a rat calvaria defect model over 6 weeks, with comparisons made against empty defects and grafts lacking hBMP-2. Micro-computed tomography analysis revealed improved bone regeneration parameters in the hBMP-2 group compared with those in the graft-only group, although statistical significance was limited to the trabecular number, which approached borderline significance (p < 0.1). Histological analysis corroborated these findings, revealing significantly enhanced new bone formation but only a reducing tendency of residual graft material in the hBMP-2 group. This study presents a promising approach for bone regeneration by utilizing genetically engineered human cells to produce BMP-2 within clinically available bone graft materials, potentially mitigating the high-dose requirements and associated complications of conventional BMP-2 therapies.