An osteophilic and fibrophobic nanocomposite hydrogel for alveolar bone defect repair

Uncontrolled soft-tissue invasion remains a major challenge in alveolar bone defect repair and is conventionally managed using guided bone regeneration membranes. However, membrane-based approaches mainly depend on passive physical exclusion and lack active tissue selectivity. Herein, we report an osteophilic and fibrophobic nanocomposite hydrogel, termed BHP-gel, composed of crosslinked gelatin and Ca(OH)₂-activated bioactive hollow particles. BHP-gel is designed to provide structural support while actively regulating early cellular competition between osteogenic and fibroblastic cells within bone defects. In vitro, BHP-gel selectively promoted the viability, migration and osteogenic differentiation of MC3T3-E1 pre-osteoblasts, accompanied by increased calcium-associated staining, while suppressing the viability and migration of L929 fibroblasts and gingival fibroblasts. Transcriptomic analysis suggested that fibroblastic inhibition was associated with downregulated migration-related genes and altered apoptosis-related transcriptional responses, whereas BHP-treated MC3T3-E1 cells showed upregulated genes related to migration, calcium signaling, and Wnt-associated osteogenic regulation. In a rat alveolar bone defect model, BHP-gel improved micro-CT-derived indices of mineralized tissue formation and trabecular microarchitecture compared with the control, HP-gel, and Bio-Oss® groups. These findings suggest that BHP-gel supports bone repair and exhibits cell-type-dependent regulation of osteogenic and fibroblastic cells in vitro, providing a materials-based strategy that may reduce reliance on exogenous barrier membranes for alveolar bone defect repair.