A dual-functional hydrogel scaffold promotes periodontal bone regeneration through stem cell recruitment and osteogenic growth peptide delivery.

Periodontal bone destruction continues to be a leading cause of tooth loss in periodontitis, underscoring the need for novel regenerative approaches. Although mesenchymal stem cells (MSCs) possess multipotent differentiation capacity that supports bone repair, existing scaffold systems fail to provide targeted recruitment and sustained osteoinductive signals. To address this, we engineered a bone-targeting hydrogel functionalized with osteogenic growth peptide (OGP)-and bone-targeting YLL3 motifs (OGP-HAMA-YLL3), enabling spatiotemporal control of stem cell homing and osteogenic differentiation. Systematic evaluation via subcutaneous transplantation in Balb/c nude mice revealed that this dual-functional biomaterial significantly enhances ectopic bone formation, as confirmed by histological analyses. In rat alveolar bone defect models, OGP-HAMA-YLL3 significantly increased new bone volume and mineralization density at 8 weeks after implantation. Notably, in a clinically relevant minipig periodontitis model, the hydrogel scaffold achieved higher bone defect regeneration with concomitant reduction of inflammatory cytokines (IL-1β, TNF-α) while maintaining favorable biosafety profiles in vital organs. As a cell-free therapeutic platform, OGP-HAMA-YLL3 demonstrates translational potential for functional periodontal reconstruction through biomimetic regulation of endogenous stem cell behavior.