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Glucose-responsive nanozyme hydrogel for glycemic control and catalytic anti-infective therapy in diabetic wound healing

Qi-Dong TaiDepartment of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, ChinaYuan TangState Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200433, ChinaSong-tao XIEInstitute for Engineering Medicine, Kunming Medical University, Kunming, 650500, ChinaYu-Yun YeInstitute for Engineering Medicine, Kunming Medical University, Kunming, 650500, ChinaXikang TangDepartment of Pediatrics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, ChinaQiunan LyuDepartment of Orthopedics, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, ChinaZhijin FanInstitute for Engineering Medicine, Kunming Medical University, Kunming, 650500, ChinaYuhui LiaoInstitute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China

2025en

ABI

Annotatsiya

Diabetes-induced impairment in glycemic regulation delays wound healing by promoting bacterial infection, oxidative stress, and vascular injury. To address these challenges, we developed a glucose-activated, self-switchable nanozyme–hydrogel platform capable of intelligent, on-demand insulin release synchronized with blood glucose fluctuations, thereby achieving closed-loop glycemic control while promoting tissue repair. This multifunctional system integrates glucose oxidase (GOx) and insulin within bimetallic Zn-Fe metal organic framework nanoparticles (MOF(Zn-Fe)/GOx/INS), which are embedded in a ROS-responsive hydrogel. Under hyperglycemic conditions, GOx catalyzes glucose oxidation to gluconic acid and H 2 O 2 , generating a mildly acidic microenvironment. This acidity triggers the peroxidase-like activity of MOF(Zn-Fe) to produce hydroxyl radicals (•OH), enabling potent antibacterial effects and accelerating MOF degradation, thereby releasing insulin to restore normoglycemia. As glucose levels normalize, catalytic activity is self-terminated to prevent hypoglycemia. In vitro and in vivo studies confirmed robust antibacterial performance, enhanced angiogenesis, anti-inflammatory activity, and accelerated wound closure. Transcriptomic profiling further revealed upregulation of regenerative pathways and suppression of inflammatory and apoptotic signaling. This glucose-activated autonomous system provides a powerful strategy for diabetic wound management through synergistic glycemic control, anti-infection efficacy, and tissue regeneration. Diabetes-impaired healing arises from infection, oxidative stress, and vascular injury. We designed a glucose-activated, self-switchable nanozyme–hydrogel integrating MOF(Zn-Fe)/GOx/INS for closed-loop insulin release. Hyperglycemia triggers antibacterial •OH generation and insulin release, while normoglycemia halts catalysis. This system achieves glycemic regulation, infection control, angiogenesis, and tissue repair, offering a synergistic strategy for diabetic wound management.

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DOI: 10.1016/j.mtbio.2025.102405

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