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The hyperglycemic microenvironment triggers oxidative stress, microbial dysbiosis, and impaired angiogenesis, thereby disrupting the normal wound\u2010healing process. Despite recent advancements, diabetic ulcers remain resistant to healing, leading to high amputation rates, which require novel treatments. Conventional therapies often fail to adequately address these multifaceted issues. Nanozymes, engineered nanoparticles that exhibit enzyme\u2010like activities, are promising alternatives to natural enzymes for managing diabetic wounds. They offer sustained catalytic control over glucose, hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ), and reactive oxygen species (ROS) in chronic wounds. Their stability, tailorable catalytic profiles, and responsiveness to microenvironmental cues enable precise, on\u2010demand intervention at the wound site. This review focuses on glucose oxidase (Gox)\u2010, superoxide dismutase (SOD)\u2010, catalase (CAT)\u2010, and peroxidase (POD)\u2010mimicking nanozymes, analyzing their roles in (i) glycemic control, (ii) ROS neutralization, (iii) antimicrobial activity, and (iv) pro\u2010angiogenic signaling. It also examines advanced delivery platforms that enhance therapeutic efficacy and discusses design principles for multienzyme cascade systems. Finally, translational challenges related to biocompatibility and regulatory compliance are critically assessed. A roadmap integrating artificial intelligence\u2010driven multimodal therapy with personalized precision medicine further optimizes the clinical applications of nanozyme in treating chronic diabetic wounds.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202504482","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T08:40:47Z","timestamp":1763800847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Breaking the Vicious Cycle: Nanozyme\u2010Driven Multimodal Therapeutics for Diabetic Wound Regeneration"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1126-1040","authenticated-orcid":false,"given":"Muhammad","family":"Touqeer","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Research Center for Nano\u2010biomaterials &amp; Regenerative Medicine College of Artificial Intelligence Taiyuan University of Technology  Taiyuan P. 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