Photothermal-responsive nanocomposite hydrogel for intelligent drug release and alveolar bone regeneration

Abstract

The delay in diabetic alveolar bone repair is primarily attributed to abnormal osteogenic differentiation. Traditional pharmacological therapy struggles to provide effective bone regeneration due to the poor bioavailability of medicine. Currently, a synergistic effect of pharmacological and photothermal therapy holds potential for bone repair. Herein, a photothermal-responsive nanocomposite hydrogel capable of inducing osteogenic differentiation was proposed for diabetic alveolar bone damage. Phloretin and strontium (Sr) ions coordinated to form a metal-phenolic network, which was then coated with a polydopamine layer to form composite nanoparticles (P@PSr NPs). Benefiting from a thiourea-ferric ion chelation hydrogel as the carrier, P@PSr NPs were anchored into the network through hydrazone and metal-coordination bonds to form HNA@P@PSr hydrogel. The construction of dual dynamic crosslinking enabled on-demand and spatiotemporally controlled release of P@PSr NPs. HNA@P@PSr demonstrated mild photothermal performance under near-infrared (NIR) irradiation. NIR radiation triggered the cleavage of hydrazone bonds, releasing nanoparticles. Meanwhile, metal coordination bonds maintained network integrity, preventing instantaneous gel collapse. Early on-demand release of nanoparticles could exert antibacterial and anti-inflammatory effects, while sustained Sr2+ release achieved long-term osteogenic induction. Importantly, HNA@P@PSr effectively reduced excessive intracellular ROS levels and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells. In a rat model of diabetic alveolar bone defects, HNA@P@PS effectively attenuated alveolar bone loss by enhancing bone density, collagen deposition, and angiogenesis. In summary, HNA@P@PSr integrated NIR irradiation markedly promotes alveolar bone regeneration, making it a potential strategy for the treatment of diabetic alveolar bone defects.