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Factors like hyperglycemia, oxidative stress, impaired angiogenesis and excessive inflammation contribute to the delayed healing trajectory. Mounting evidence indicates a close association between impaired mitochondrial function and diabetic complications, including chronic wounds. Mitochondria are critical for providing energy essential to wound healing processes. However, mitochondrial dysfunction exacerbates other pathological factors, creating detrimental cycles that hinder healing. This study conducted correlation analysis using clinical specimens, revealing a positive correlation between mitochondrial dysfunction and oxidative stress, inflammatory response and impaired angiogenesis in diabetic wounds. Restoring mitochondrial function becomes imperative for developing targeted therapies. Herein, we synthesized a biodegradable poly (glycerol sebacate)\u2010based multiblock hydrogel, named poly (glycerol sebacate)\u2010co\u2010poly (ethylene glycol)\u2010co\u2010poly (propylene glycol) (PEPGS), which can be degraded in vivo to release glycerol, a crucial component in cellular metabolism, including mitochondrial respiration. We demonstrate the potential of PEPGS\u2010based hydrogels to improve outcomes in diabetic wound healing by revitalizing mitochondrial metabolism. Furthermore, we investigate the underlying mechanism through proteomics analysis, unravelling the regulation of ATP and nicotinamide adenine dinucleotide metabolic processes, biosynthetic process and generation during mitochondrial metabolism. These findings highlight the therapeutic potential of PEPGS\u2010based hydrogels as advanced wound dressings for diabetic wound healing.<\/jats:p>","DOI":"10.1111\/cpr.13613","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T05:50:31Z","timestamp":1707889831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A bioenergetically\u2010active ploy (glycerol sebacate)\u2010based multiblock hydrogel improved diabetic wound healing through revitalizing mitochondrial metabolism"],"prefix":"10.1111","volume":"57","author":[{"given":"Xin","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai 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