The injectable cationic double-crosslinked hydrogel facilitates bone regeneration and repair through sustained antibacterial activity

Due to the barrier effect of dental plaque and the growing issue of antibiotic resistance, the efficacy of conventional antimicrobial agents against oral pathogens has progressively declined. Chronic periodontal infections are recalcitrant to eradication and exert inhibitory effects on bone repair and regeneration, representing one of the primary challenges in the management of periodontitis-induced bone defects. In this study, we developed an injectable cationic photopolymerizable dual-crosslinked O-HAMA/GelMA/PLL hydrogel. The aldehyde groups on oxidized HAMA undergo a Schiff base reaction with the amino groups of ε-polylysine (ε-PLL), forming dynamic crosslinks. Subsequently, blue light triggers a radical polymerization of the double bonds present in GelMA and O-HAMA, creating a secondary layer of covalent crosslinks. This dual-crosslinked structure enables the sustained release of the cationic antimicrobial peptide ε-PLL for up to 14 days, demonstrating superior controlled-release properties. Furthermore, the hydrogel exhibits excellent biocompatibility and enhanced mechanical strength, thus fulfilling the requirements for clinical applications. The in vivo bone repair efficacy was assessed using rat cranial defect and periodontitis models. The results indicated that the O-HAMA/GelMA/PLL hydrogel improves the inflammatory microenvironment through sustained antibacterial activity and promotes bone tissue regeneration. This strategy offers strong antibacterial performance and shows promising potential for the repair of alveolar bone defects caused by periodontitis.