Polyphenol‐Metal Mediated Mitochondrial‐Targeted Injectable Hydrogel Promotes Diabetic Wound Healing

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Main Authors: Xiangcun Shang, Yan Wang, Wenhuan Huang, Cong Li, Kaizei Su, Jingwei Jin, Dongli Li, Keke Wu, Panpan Wu
Format: Artículo Open Access
Published: Wiley 2026
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author Xiangcun Shang
Yan Wang
Wenhuan Huang
Cong Li
Kaizei Su
Jingwei Jin
Dongli Li
Keke Wu
Panpan Wu
author_facet Xiangcun Shang
Yan Wang
Wenhuan Huang
Cong Li
Kaizei Su
Jingwei Jin
Dongli Li
Keke Wu
Panpan Wu
Xiangcun Shang
Yan Wang
Wenhuan Huang
Cong Li
Kaizei Su
Jingwei Jin
Dongli Li
Keke Wu
Panpan Wu
collection Wiley Open Access
contents Polyphenol‐Metal Mediated Mitochondrial‐Targeted Injectable Hydrogel Promotes Diabetic Wound Healing Xiangcun Shang Yan Wang Wenhuan Huang Cong Li Kaizei Su Jingwei Jin Dongli Li Keke Wu Panpan Wu Advanced Healthcare Materials ABSTRACT Diabetic wounds present significant therapeutic challenges, characterized by persistent inflammation, impaired vascular regeneration, and mitochondrial dysfunction, which collectively contribute to delayed healing and a high recurrence rate. To address these limitations, we developed an injectable hydrogel dressing composed of gelatin methacrylate (GelMA), alginate methacrylate (AlgMA), and tannic acid‐cobalt ion (TACo) nanoparticles, cross‐linked through photopolymerization. The resulting hydrogel exhibited favorable physical properties and pH‐responsive release behavior, enabling the sustained release of bioactive components in the acidic wound microenvironment. The hydrogel exhibited outstanding multifunctionality, characterized by a potent free radical scavenging capacity that effectively mitigated oxidative stress. Moreover, it displayed broad‐spectrum antibacterial activity against common pathogens including E. coli and S. aureus , and promoted macrophage reprogramming into the pro‐regenerative M2 phenotype, thereby addressing chronic inflammation. TACo exhibited efficient mitochondrial targeting capability, preserved mitochondrial membrane integrity, and significantly reduced mitochondrial oxidative stress. In a diabetic rat wound model, hydrogel treatment markedly promoted tissue regeneration by accelerating re‐epithelialization, improving collagen architecture, and enhancing the expression of key angiogenic markers, including CD31 and VEGF. Overall, these findings highlight the hydrogel's capacity to concurrently mitigate oxidative stress, resolve inflammatory dysregulation, and restore mitochondrial function, supporting its potential as a promising advanced therapy for refractory diabetic wounds. 10.1002/adhm.71249 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/adhm.71249
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id wiley_oa_10_1002_adhm_71249
institution Wiley Open Access
license_str_mv http://onlinelibrary.wiley.com/termsAndConditions#vor
publishDate 2026
publisher Wiley
record_format wiley_oa
spellingShingle Polyphenol‐Metal Mediated Mitochondrial‐Targeted Injectable Hydrogel Promotes Diabetic Wound Healing
Xiangcun Shang
Yan Wang
Wenhuan Huang
Cong Li
Kaizei Su
Jingwei Jin
Dongli Li
Keke Wu
Panpan Wu
Advanced Healthcare Materials
Polyphenol‐Metal Mediated Mitochondrial‐Targeted Injectable Hydrogel Promotes Diabetic Wound Healing Xiangcun Shang Yan Wang Wenhuan Huang Cong Li Kaizei Su Jingwei Jin Dongli Li Keke Wu Panpan Wu Advanced Healthcare Materials ABSTRACT Diabetic wounds present significant therapeutic challenges, characterized by persistent inflammation, impaired vascular regeneration, and mitochondrial dysfunction, which collectively contribute to delayed healing and a high recurrence rate. To address these limitations, we developed an injectable hydrogel dressing composed of gelatin methacrylate (GelMA), alginate methacrylate (AlgMA), and tannic acid‐cobalt ion (TACo) nanoparticles, cross‐linked through photopolymerization. The resulting hydrogel exhibited favorable physical properties and pH‐responsive release behavior, enabling the sustained release of bioactive components in the acidic wound microenvironment. The hydrogel exhibited outstanding multifunctionality, characterized by a potent free radical scavenging capacity that effectively mitigated oxidative stress. Moreover, it displayed broad‐spectrum antibacterial activity against common pathogens including E. coli and S. aureus , and promoted macrophage reprogramming into the pro‐regenerative M2 phenotype, thereby addressing chronic inflammation. TACo exhibited efficient mitochondrial targeting capability, preserved mitochondrial membrane integrity, and significantly reduced mitochondrial oxidative stress. In a diabetic rat wound model, hydrogel treatment markedly promoted tissue regeneration by accelerating re‐epithelialization, improving collagen architecture, and enhancing the expression of key angiogenic markers, including CD31 and VEGF. Overall, these findings highlight the hydrogel's capacity to concurrently mitigate oxidative stress, resolve inflammatory dysregulation, and restore mitochondrial function, supporting its potential as a promising advanced therapy for refractory diabetic wounds. 10.1002/adhm.71249 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Polyphenol‐Metal Mediated Mitochondrial‐Targeted Injectable Hydrogel Promotes Diabetic Wound Healing
topic Advanced Healthcare Materials
url https://advanced.onlinelibrary.wiley.com/doi/10.1002/adhm.71249