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Bacteria-responsive programmed self-activating antibacterial hydrogel to remodel regeneration microenvironment for infected wound healing

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National Science Review 2024年第4期11卷 254-270页

作者： Yutong Yang Jiaxin Wang Shengfei Huang Meng Li Jueying Chen Dandan Pei Zhen Tang Baolin Guo State Key Laboratory for Mechanical Behavior of Materials and Frontier Institute of Science and Technology and Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of Stomatology Xi'an Jiaotong University Department of Orthopedics Tangdu Hospital Fourth Military Medical University Department of Orthopedics The First Affiliated Hospital of Xi'an Jiaotong University

There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing. Specifically, p H-responsive H2O2self-supplying composite nanozyme（MSCO） and p H/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase（PPEL） were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan（CA） and phenylboronic acid-modified oxidized dextran（ODP） to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide（NO） release. The composite hydrogel showed 'self-diagnostic' treatment for changes in the wound *** self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new method for the design of intelligent wound dressings.

关键词： bacterial response hydrogel dressing multiple nanozyme activity biofilm elimination infected motion wound healing

Antimicrobial hydrogel with multiple pH-responsiveness for infected burn wound healing

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Nano Research 2023年第8期16卷 11139-11148页

作者： Na Li Wan Liu Xiaoyan Zheng Qing Wang Lixin Shen Junfeng Hui Daidi Fan Shaanxi Key Laboratory of Degradable Biomedical Materials Shaanxi R&D Center of Biomaterials and Fermentation EngineeringSchool of Chemical EngineeringNorthwest UniversityXi’an 710069China Biotech.&Biomed.Research Institute Northwest UniversityXi’an 710069China The college of life sciences Northwest UniversityXi’an 710069China

Burns are a common medical problem globally,and wound infection is one of the major causes of inducing related *** antibiotics effectively prevent wound infections,the misuse of antibiotics has created a new problem of ***,we propose a new strategy to obtain pH-responsive antimicrobial P-ZIF(ZIF:zeolitic imidazolate framework)by loading polyhexamethylenebiguanide(PHMB)into the framework of ZIF-8 *** will enable PHMB to be released in the weak acid environment of an infected *** address burn infections,P-ZIF nanoparticles were loaded into a hydrogel system made of sodium alginate(SA)and 3-aminophenylboronic acid modified human-like collagen(H-A)through borate ester *** resulting H-A/SA/P-ZIF(HASPZ)hydrogel dressing not only possesses antibacterial and wound healing properties but also has dual pH responsiveness to prevent the overuse of medication while effectively treat deep second-degree ***,P-ZIF nanoparticles and the corresponding HASPZ hydrogel dressing are considered of significant importance in antimicrobial,drug delivery,and wound repair.

关键词： P-ZIF nanoparticles hydrogel dressing antibacterial pH-responsive burn wound healing

Macrophage metabolism reprogramming EGCG-Cu coordination capsules delivered in polyzwitterionic hydrogel for burn wound healing and regeneration

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Bioactive Materials 2023年第11期29卷 251-264页

作者： Qinghua Li Huijuan Song Shuangyang Li Pengbo Hu Chuangnian Zhang Ju Zhang Zujian Feng Deling Kong Weiwei Wang Pingsheng Huang Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China Institute of Radiation Medicine Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China Department of Polymer Science and Engineering Key Laboratory of Systems BioengineeringSchool of Chemical Engineering and TechnologyTianjin UniversityTianjin300072China Emergency Department of Binzhou Medical University Hospital BinzhouShandong Province256600China State Key Laboratory of Medicinal Chemical Biology College of Life SciencesNankai UniversityTianjin300071China

Excessive reactive oxygen species(ROS)at severe burn injury sites may promote metabolic reprogramming of macrophages to induce a deteriorative and uncontrolled inflammation cycle,leading to delayed wound healing and ***,a novel bioactive,anti-fouling,flexible polyzwitterionic hydrogel encapsulated with epigallocatechin gallate(EGCG)-copper(Cu)capsules(termed as EGCG-Cu@CBgel)is engineered for burn wound management,which is dedicated to synergistically exerting ROS-scavenging,immune metabolic regulation and pro-angiogenic ***-Cu@CBgel can scavenge ROS to normalize intracellular redox homeostasis,effectively relieving oxidative damages and blocking proinflammatory signal ***,EGCG-Cu can inhibit the activity of hexokinase and phosphofructokinase,alleviate accumulation of pyruvate and convert it to acetyl coenzyme A(CoA),whereby inhibits glycolysis and normalizes tricarboxylic acid(TCA)***,metabolic reprogramming of macrophages by EGCG-Cu downregulates M1-type polarization and the expression of proinflammatory cytokines both in vitro and in ***,copper ions(Cu^(2+))released from the hydrogel facilitate ***-Cu@CBgel significantly accelerates the healing of severe burn wound via promoting wound closure,weakening tissue-damaging inflammatory responses and enhancing the remodeling of pathological ***,this study demonstrates the great potential of bioactive hydrogel dressing in treating burn wounds without unnecessary secondary damage to newly formed skin,and highlights the importance of immunometabolism modulation in tissue repair and regeneration.

关键词： ROS scavenging hydrogel dressing EGCG-Cu capsule Metabolic reprogramming Burn wound healing

Microenvironment responsive nanocomposite hydrogel with NIR photothermal therapy,vascularization and anti-inflammation for diabetic infected wound healing

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Bioactive Materials 2023年第8期26卷 306-320页

作者： Shuangli Zhu Bangjiao Zhao Maocai Li Hao Wang Jiayi Zhu Qingtao Li Huichang Gao Qi Feng Xiaodong Cao School of Materials Science and Engineering South China University of TechnologyGuangzhou510641PR China National Engineering Research Centre for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou510006PR China School of Medicine South China University of TechnologyGuangzhou510006PR China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou510006PR China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou510006PR China Zhongshan Institute of Modern Industrial Technology of SCUT ZhongshanGuangdong528437PR China

Bacterial infection,excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic *** present,most of wound repair materials are passive and can’t response to the wound microenvironment,resulting in a low utilization of bioactive substances and hence a poor therapeutic ***,it’s essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of *** this work,metformin-laden CuPDA NPs composite hydrogel(Met@CuPDA NPs/HG)was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine(Gel-DA),Cu-loaded polydopamine nanoparticles(CuPDA NPs)with hyaluronic acid modified by phenyl boronate acid(HA-PBA),which possessed good injectability,self-healing,adhesive and DPPH scavenging *** slow release of metformin was achieved by the interaction with CuPDA NPs,boric groups(B-N coordination)and the constraint of hydrogel *** had a pH and glucose responsive release behavior to treat different wound microenvironment ***,CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of>95%within 10 min and also the slow release of Cu^(2+)to protect wound from infection for a long ***@CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu^(2+).More importantly,Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB *** experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria,inhibiting inflammation,improving angiogenesis and accelerating the deposition of ECM and ***,Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.

关键词： Diabetic ulcer hydrogel dressing Cu-loaded polydopamine nanoparticles Metformin Photothermal responsiveness Angiogenesis and anti-inflammation

Breathable,antifreezing,mechanically skin-like hydrogel textile wound dressings with dual antibacterial mechanisms

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Bioactive Materials 2023年第3期21卷 313-323页

作者： Sihan Jiang Jiajia Deng Yuhui Jin Bo Qian Wanqi Lv Qiangqiang Zhou Enhua Mei Rasoul Esmaeely Neisiany Yuehua Liu Zhengwei You Jie Pan Department of Orthodontics Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghai200001PR China Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases Fudan UniversityShanghai200001PR China State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and EngineeringInstitute of Functional MaterialsResearch Base of Textile Materials for Flexible Electronics and Biomedical Applications(China Textile Engineering Society)Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative MedicineDonghua UniversityShanghai201620PR China Department of Endodontics Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghai200001PR China Department of Materials and Polymer Engineering Faculty of EngineeringHakim Sabzevari UniversitySabzevar***Iran

hydrogels are emerging as the most promising dressings due to their excellent biocompatibility,extracellular matrix mimicking structure,and drug loading ***,existing hydrogel dressings exhibit limited breathability,poor environmental adaptability,potential drug resistance,and limited drug options,which extremely restrict their therapeutic effect and working ***,the current research introduces the first paradigm of hydrogel textile dressings based on novel gelatin glycerin hydrogel(glyhydrogel)fibers fabricated by the Hofmeister effect based wet *** from the unique knitted structure,the textile dressing features excellent breathability(1800 times that of the commercially available 3 M dressing)and stretchability(535.51±38.66%).Furthermore,the glyhydrogel textile dressing can also withstand the extreme temperature of-80℃,showing the potential for application in subzero ***,the introduction of glycerin endows the textile dressing with remarkable antibacterial property and expands the selection of loaded drugs(e.g.,clindamycin).The prepared glyhydrogel textile dressing shows an excellent infected wound healing effect with a complete rat skin closure within 14 *** these functions have not been achievable by traditional hydrogel dressings and provide a new approach for the development of hydrogel dressings.

关键词： hydrogel textile hydrogel dressing Breathable Dual antibacterial Skin regeneration