Geometry-Dependent Osteogenic Performance of Demineralized Dentin Matrix as a Carrier for rhBMP-2

Abstract BACKGROUND : Demineralized dentin matrix (DDM) is a bioactive collagen-based scaffold with intrinsic osteoinductive properties and potential as a carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2). However, the influence of DDM geometry on its osteogenic performance and carrier efficiency remains unclear. This study aimed to evaluate the geometry-dependent osteogenic efficacy of DDM and its role as an rhBMP-2 delivery system. METHODS : DDM was prepared in particulate (300–800 µm) and block forms (root segments with drilled pores) and compared with an absorbable collagen sponge in a subcutaneous implantation model using nude mice. Each carrier was evaluated with no rhBMP-2 or with low-dose (1 µg) or high-dose (2 µg) rhBMP-2 at 2 and 4 weeks. New bone formation was assessed using micro-computed tomography and histological/histomorphometric analyses. RESULTS : Both forms of DDM demonstrated intrinsic osteoinductive capacity, inducing ectopic bone formation without exogenous rhBMP-2, whereas collagen alone showed negligible bone formation. Particulate DDM exhibited greater bone formation than block DDM, with the difference reaching statistical significance by 4 weeks. The addition of rhBMP-2 enhanced early bone formation, particularly at 2 weeks; however, by 4 weeks, DDM alone achieved comparable outcomes. Notably, particulate DDM with low-dose rhBMP-2 produced bone formation comparable to or greater than that achieved with high-dose rhBMP-2 in collagen carriers. Histological findings confirmed that DDM provided sustained osteogenesis with direct bone formation on the scaffold surface, while collagen carriers exhibited peripheral bone formation due to rapid rhBMP-2 release. CONCLUSION : DDM is an effective osteoinductive scaffold and a superior carrier for rhBMP-2 compared to collagen. Its osteogenic performance is geometry-dependent, with particulate DDM demonstrating enhanced bone regeneration. Importantly, DDM enables effective bone formation with reduced rhBMP-2 dosage, suggesting a safer and more efficient strategy for bone regeneration.