Kill Two Birds with One Stone: Dual‐Metal MOF‐Nanozyme‐Decorated Hydrogels with ROS‐Scavenging, Oxygen‐Generating, and Antibacterial Abilities for Accelerating Infected Diabetic Wound Healing

Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS ac...

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Veröffentlicht in:	Small (Weinheim an der Bergstrasse, Germany) Jg. 20; H. 48; S. e2403679 - n/a
Hauptverfasser:	Wei, Yun‐Jie, Chen, Heng, Zhou, Zi‐Wen, Liu, Chun‐Xiu, Cai, Chun‐Xian, Li, Jing, Yu, Xiao‐Qi, Zhang, Ji, Liu, Yan‐Hong, Wang, Na
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Germany Wiley Subscription Services, Inc 01.11.2024
Schlagworte:	Accumulation Animals Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology antibacterial Antiinfectives and antibacterials Bacterial infections Bioreactors Blood circulation Blood vessels Catalase Chitosan Chitosan - chemistry Chlorogenic acid Diabetes diabetic wound healing Dissolved oxygen Genipin Hydrogels Hydrogels - chemistry Hydrogen peroxide Hypoxia Infections Iridoids - chemistry Iridoids - pharmacology Metal-organic frameworks Metal-Organic Frameworks - chemistry Metal-Organic Frameworks - pharmacology Mice nanozymes Oxidation resistance Oxygen - chemistry Oxygenation reactive oxygen species Reactive Oxygen Species - metabolism Scavenging Wound healing Wound Healing - drug effects nanozymes antibacterial hydrogels diabetic wound healing reactive oxygen species
ISSN:	1613-6810, 1613-6829, 1613-6829
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Abstract	Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)‐crosslinked chitosan (CS)‐based hydrogels decorated with the biomimetic metal–organic framework (MOF)‐nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP‐CS (MCGC), are prepared. With catalase (CAT)‐like activity, these dual‐metal MOF‐nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H2O2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management. The metal‐organic framework (MOF)‐nanozyme‐decorated hydrogel with injectable, adhesive, and self‐healing properties, named MOF/CGA@GP‐CS (MCGC), is constructed. The antibacterial hydrogel exhibits nanozyme‐mediated catalase (CAT)‐like performance, simultaneously facilitating reactive oxygen species (ROS)‐scavenging and oxygen‐generation in infected diabetic wounds. Promisingly, the MCGC hydrogel significantly promotes wound closure, improves collagen deposition, and alleviates inflammation for accelerating infected diabetic wound healing in vivo.
AbstractList	Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)‐crosslinked chitosan (CS)‐based hydrogels decorated with the biomimetic metal–organic framework (MOF)‐nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP‐CS (MCGC), are prepared. With catalase (CAT)‐like activity, these dual‐metal MOF‐nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H 2 O 2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management. Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)-crosslinked chitosan (CS)-based hydrogels decorated with the biomimetic metal-organic framework (MOF)-nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP-CS (MCGC), are prepared. With catalase (CAT)-like activity, these dual-metal MOF-nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H O into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management. Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)-crosslinked chitosan (CS)-based hydrogels decorated with the biomimetic metal-organic framework (MOF)-nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP-CS (MCGC), are prepared. With catalase (CAT)-like activity, these dual-metal MOF-nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H2O2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management.Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)-crosslinked chitosan (CS)-based hydrogels decorated with the biomimetic metal-organic framework (MOF)-nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP-CS (MCGC), are prepared. With catalase (CAT)-like activity, these dual-metal MOF-nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H2O2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management. Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)‐crosslinked chitosan (CS)‐based hydrogels decorated with the biomimetic metal–organic framework (MOF)‐nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP‐CS (MCGC), are prepared. With catalase (CAT)‐like activity, these dual‐metal MOF‐nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H2O2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management. Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)‐crosslinked chitosan (CS)‐based hydrogels decorated with the biomimetic metal–organic framework (MOF)‐nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP‐CS (MCGC), are prepared. With catalase (CAT)‐like activity, these dual‐metal MOF‐nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H2O2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management. The metal‐organic framework (MOF)‐nanozyme‐decorated hydrogel with injectable, adhesive, and self‐healing properties, named MOF/CGA@GP‐CS (MCGC), is constructed. The antibacterial hydrogel exhibits nanozyme‐mediated catalase (CAT)‐like performance, simultaneously facilitating reactive oxygen species (ROS)‐scavenging and oxygen‐generation in infected diabetic wounds. Promisingly, the MCGC hydrogel significantly promotes wound closure, improves collagen deposition, and alleviates inflammation for accelerating infected diabetic wound healing in vivo.
Author	Zhou, Zi‐Wen Zhang, Ji Liu, Yan‐Hong Cai, Chun‐Xian Yu, Xiao‐Qi Liu, Chun‐Xiu Li, Jing Wei, Yun‐Jie Chen, Heng Wang, Na
Author_xml	– sequence: 1 givenname: Yun‐Jie surname: Wei fullname: Wei, Yun‐Jie organization: Sichuan University – sequence: 2 givenname: Heng surname: Chen fullname: Chen, Heng organization: Sichuan University – sequence: 3 givenname: Zi‐Wen surname: Zhou fullname: Zhou, Zi‐Wen organization: Sichuan University – sequence: 4 givenname: Chun‐Xiu surname: Liu fullname: Liu, Chun‐Xiu organization: Sichuan University – sequence: 5 givenname: Chun‐Xian surname: Cai fullname: Cai, Chun‐Xian organization: Sichuan University – sequence: 6 givenname: Jing surname: Li fullname: Li, Jing organization: Sichuan University – sequence: 7 givenname: Xiao‐Qi surname: Yu fullname: Yu, Xiao‐Qi organization: Sichuan University – sequence: 8 givenname: Ji surname: Zhang fullname: Zhang, Ji organization: Sichuan University – sequence: 9 givenname: Yan‐Hong surname: Liu fullname: Liu, Yan‐Hong email: yanhongliu@scu.edu.cn organization: Sichuan University – sequence: 10 givenname: Na orcidid: 0000-0002-1703-1124 surname: Wang fullname: Wang, Na email: wnchem@scu.edu.cn organization: Sichuan University
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/39240068$$D View this record in MEDLINE/PubMed
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Snippet	Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection,...
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SubjectTerms	Accumulation Animals Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology antibacterial Antiinfectives and antibacterials Bacterial infections Bioreactors Blood circulation Blood vessels Catalase Chitosan Chitosan - chemistry Chlorogenic acid Diabetes diabetic wound healing Dissolved oxygen Genipin Hydrogels Hydrogels - chemistry Hydrogen peroxide Hypoxia Infections Iridoids - chemistry Iridoids - pharmacology Metal-organic frameworks Metal-Organic Frameworks - chemistry Metal-Organic Frameworks - pharmacology Mice nanozymes Oxidation resistance Oxygen - chemistry Oxygenation reactive oxygen species Reactive Oxygen Species - metabolism Scavenging Wound healing Wound Healing - drug effects
Title	Kill Two Birds with One Stone: Dual‐Metal MOF‐Nanozyme‐Decorated Hydrogels with ROS‐Scavenging, Oxygen‐Generating, and Antibacterial Abilities for Accelerating Infected Diabetic Wound Healing
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