Synergistic enhancement of skull bone regeneration in rats using demineralized dentin matrix dual-loaded with BMP-2 and NELL-1 growth factors

To address the limitations associated with current bone graft materials, particularly the slow resorption of deproteinized bovine bone minerals and the adverse effects of high-dose BMP-2, we developed an innovative tripartite regeneration platform. This platform employs a decalcified dentin matrix (DDM) as a physiological carrier for the spatio-temporal co-delivery of BMP-2 and Nell-1, representing a novel combined strategy. The DDM particles, optimized to a size range of 500-1000 μm through EDTA hierarchical decalcification (achieving 70% decalcification), exhibited a marked increase in pulp tubule diameter, cross-sectional area, and porosity. Scanning electron microscopy (SEM) analysis confirmed that the absence of a smear layer and the presence of uniform tubules facilitated osteoblast infiltration. In a rat model with critical-sized skull defects, the synergistic DBN structure (comprising DDM, BMP-2, and NELL-1) resulted in nearly complete bone regeneration within 8 weeks, significantly enhancing bone volume and bone mineral density. This bionic platform addresses the "bone-induced inflammation paradox" by utilizing the hierarchical topological structure of DDM and the synergistic dynamics of two factors: the rapid release of BMP-2 and the sustained release of NELL-1. This approach surpasses the clinical gold standard and satisfies the FDA's efficacy criteria for the repair of critical size defects.