Yao Lin, Baicheng Xing, Xiong Zhang, Guanghua Lu, Huaiyuan Zhang, Yuxin Zhang, Xingchao Wang, Ziyan Zhang, Zhong Wang, Ying Zhang, Yong Gao, Chunrui Yang, Junyan Zhang, Wenyu Qiao, Yufeng Zhou
Diabetic wound infections remain highly refractory to treatment due to persistent bacterial colonization, oxidative stress, dysregulated inflammation, vascular insufficiency, and impaired extracellular-matrix remodeling. Current therapeutic strategies remain limited by poor tissue penetration, inadequate infection control, and ineffective inflammatory-oxidative microenvironment modulation. Here, we engineered a sonosensitive antimicrobial peptide composite hydrogel, FFRK8@ZnO2@fHAMA, by integrating human host-defense-peptide-derived FFRK8, microenvironment-responsive ZnO2 microspheres, and fish-collagen-modified hyaluronic acid methacrylate (fHAMA) into an injectable bioactive matrix. Upon low-intensity pulsed ultrasound (LIPUS) irradiation, this hydrogel acts as a multifunctional regenerative dressing that couple broad-spectrum bacterial eradication with oxidative-stress attenuation, macrophage repolarization, angiogenic activation and extracellular-matrix reconstruction. Distinct from conventional passive dressings or antibiotic-dependent therapies, FFRK8@ZnO2@fHAMA enables non-invasive and spatiotemporally precise activation, sustained local therapeutic retention and coordinated immune-redox-metabolic microenvironment remodeling while maintaining favorable biosafety. This sonosensitive peptide hydrogel offers a powerful bioactive strategy for repairing infected diabetic wound and may inspire next-generation therapeutic modality for chronic non-healing tissue regeneration.