Nanohybrid Hydrogel with Dual Functions: Controlled Low‐Temperature Photothermal Antibacterial Activity and Promoted Regeneration for Treating MRSA‐Infected Bone Defects

Methicillin-resistant Staphylococcus aureus (MRSA)-related bone defects pose significant clinical challenges due to treatment failures. Here, an injectable nanohybrid hydrogel (FND-ZHD) is developed that combines controlled low-temperature photothermal antibacterial therapy with enhanced bone regeneration. The hydrogel uses Pluronic F-127 as the matrix, incorporating polydopamine-coated nano-hydroxyapatite and zinc oxide nanoparticles encapsulated with polydopamine and hyaluronic acid, forming a sophisticated nanostructured composite. Under near-infrared (NIR) irradiation, the FND-ZHD hydrogel exhibits efficient photothermal properties, enabling precise low-temperature photothermal therapy to eliminate MRSA infections. The photothermal process generates reactive oxygen species (ROS), contributing to potent antibacterial activity, while the hydrogel design allows self-elimination of excess ROS to minimize cytotoxicity. Simultaneously, the hydrogel enhances bone regeneration by upregulating heat shock protein 70 (HSP70), promoting osteogenic differentiation and accelerating bone repair. In vitro and in vivo experiments demonstrate that the FND-ZHD hydrogel not only possesses strong antibacterial efficacy against MRSA but also significantly improves bone healing in infected bone defect models. This dual-function strategy leverages the synergistic effects of nanomaterials at the nano- and microscale, achieving simultaneous antibacterial action and bone regeneration. The work highlights the potential of nanotechnology-based multifunctional biomaterials in addressing complex medical problems, paving the way for advanced therapies in orthopedic and regenerative medicine.