Nanoarchitecture‐Integrated Hydrogel Boosts Angiogenesis–Osteogenesis–Neurogenesis Tripling for Infected Bone Fracture Healing

Infected fracture healing is a complicated process that includes intricate interactions at the cellular and molecular levels. In addition to angiogenesis and osteogenesis, the significance of neurogenesis in fracture healing has also been recognized in recent years. Here, a nanocomposite hydrogel containing pH‐responsive zinc‐gallium‐humic acids (HAs) nanoparticles is developed. Through the timed release of Zn2+, Ga3+, and HAs, the hydrogel exhibits potent antibacterial effects and promotes angiogenesis, osteogenesis, and neurogenesis. The enhanced neurogenesis further promotes angiogenesis and osteogenesis, forming a mutually supportive angiogenesis–osteogenesis–neurogenesis cycle at the fracture site. The hydrogel achieves rapid infected fracture healing and improves tissue regeneration in mice. This study proposes a comprehensive treatment approach that combines antibacterial effects with the regulation of tissue regeneration to improve infected fracture healing. A pH‐responsive nanoarchitecture‐integrated hydrogel is developed to treat drug‐resistant bacteria‐infected fracture healing. Through the controlled release of humic acids, Zn2+, and Ga3+, the hydrogel eradicates bacterial infection, alleviates oxidative stress, and promotes angiogenesis, osteogenesis, and neurogenesis, offering a whole‐course‐repair strategy to accelerate fracture healing in a MRSA‐infected fracture model.