Functional Integrated Platform Initiates Cascade Reactions for Tooth-Extraction Wound Healing and Alveolar Bone Regeneration

Wound healing and alveolar bone regeneration after tooth extraction are critical for maxillofacial esthetics and health. Developing versatile scaffolds with clinical translatability is of great importance but is challenging for tooth-extraction management. Herein, we develop a fibrin-based versatile platform for wound healing and bone regeneration after tooth extraction. This platform is fabricated by biomineralization of glucose oxidase (GOx), l-arginine, and metronidazole into calcium phosphate nanoparticles, which are further encapsulated in fibrin. After being implanted into the extraction sockets, the platform undergoes <i>in situ</i> gelation for effective hemostasis. Within the gel, GOx catalyzes glucose to generate H₂O₂ and creates an acidic microenvironment, which subsequently oxidizes l-arginine to generate nitric oxide. Under an acidic microenvironment, the nanoparticles are degraded, resulting in the release of the antibiotic. This cascade reaction sequence enables the platform to combat bacterial infection during the initial healing stages while promoting both angiogenesis and ossification during later bone regeneration stages. Both <i>in vitro</i> and <i>in vivo</i> studies have demonstrated the superior properties of the platform in hemostasis, antibacterial activity, angiogenesis, and bone regeneration, demonstrating its tremendous potential as a comprehensive therapeutic strategy for tooth-extraction socket management.