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Peroxidase-like nanozyme based microenvironment-responsive injectable hydrogel for bacteria-infected wound healing

Science China Technological Sciences 2024年第10期67卷 3247-3260页

作者： ZHOU Wei LI XiaNan TANG MengCheng PAN LingFeng WANG BeiBei ZHANG Hao ZHANG Han WANG ShiBo KONG XiangDong Institute of Smart Biomaterial Materials School of Materials Science and EngineeringZhejiang University of Science & Technology Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering Zhejiang University of Science & Technology

hydrogel stands out as one of the most attractive wound dressings due to its excellent moisturizing properties and capacity to absorb wound exudates. However, conventional hydrogel dressings often lack responsiveness to the microenvironment, merely acting as protective barriers for the wound. Consequently, they exhibit limited effectiveness in preventing infection and facilitating wound repair. To address these problems, we have developed a multifunctional injectable hydrogel, CF/MS@HG, based on peroxidase-like nanozymes, aiming at rapidly healing bacterial-infected wounds. The hydrogel is mainly composed of oxidized sodium alginate, aminated gelatin, and polylysine, encapsulating MIL-101(CuFe) NPs(CF) and manganese selenide nanoparticles(MnSe2NPs, or MS NPs). After injection, the complex rapidly gelatinizes at the infected wound site through a Schiff base reaction. In vitro experiments have demonstrated the hydrogel's strong adhesion and self-healing ***, CF exhibiting peroxidase(POD)-like activity, catalyzes in situ hydrogen peroxide(H2O2) to generate highly toxic hydroxyl radicals(·OH) within the wound microenvironment, inducing oxidative damage to bacteria. Meanwhile, MS decomposes into H2Se in the slightly acidic wound microenvironment, disrupting bacterial metabolism and inhibiting *** addition of polylysine further enhances the hydrogel's antibacterial properties. In vivo experiments have shown that the hydrogel exhibits excellent biological safety and significantly promotes wound healing. This multifunctional smart hydrogel holds great promise for the treatment of bacterial-infected wounds.

关键词： peroxidase-like nanozyme manganese selenide injectable hydrogel bacterial infection wound healing

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injectable“cocktail”hydrogel with dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic effect

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SmartMat 2024年第2期5卷 43-53页

作者： Li Zhao Jiawen Xu Yao Tong Pengyu Gong Fucheng Gao Hui Li Yanyan Jiang Key Laboratory for Liquid-Solid Structural Evolution&Processing of Materials(Ministry of Education) School of Materials Science and EngineeringShandong UniversityJinanChina Department of Pathology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanChina Department of Clinical Laboratory The Second HospitalCheeloo College of MedicineShandong UniversityJinanChina

The combination of the first-line standard chemotherapeutic drug doxorubicin hydrochloride(DOX)and the molecular-targeted drug Herceptin(HCT)has emerged as a promising strategy for human epidermal growth receptor 2(HER-2)overexpressing breast cancer ***,insufficient drug accumulation and severe cardiotoxicity are two major challenges that limit its clinical ***,an in situ forming gold nanorods(AuNRs)-sodium alginate(ALG)hybrid hydrogel encapsulating DOX and HCT was engineered for tumor synergistic therapy involving injectable,dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic *** photothermal agent AuNRs,anticancer drug DOX,and anticancer antibody HCT were mixed in ALG solution,and after injection,the soluble ALG was quickly transformed into a hydrogel in the presence of Ca^(2+)in the ***,the hybrid hydrogel exhibits an extremely high photothermal conversion efficiency of 70%under 808 nm laser *** thermal effect can also provide photothermal stimulation to trigger the drug release from the gel *** addition,the drug release rate and the releasing degree are also sensitive to the *** vitro studies demonstrated that the PEI-AuNR/DOX/HCT/ALG hydrogel has facilitated the therapeutic efficiency of each payload and demonstrated a strong synergistic killing effect on SK-BR-3 *** vivo imaging results showed that the local drug delivery system can effectively reduce the nonspecific distribution in normal tissues and increase drug concentration at tumor *** proposed hydrogel system shows significant clinical implications by easily introducing a sustainable photothermal therapy and a potential universal carrier for the local delivery of multiple drugs to overcome the challenges faced in HER-2 overexpressing cancer therapy.

关键词： dual-stimuli-responsive drug release HER-2 overexpressing breast cancer injectable hydrogel photothermal therapy synergistic effect

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Advances of injectable hydrogel-based scaffolds for cartilage regeneration

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Regenerative Biomaterials 2019年第3期6卷 129-140页

作者： Jiawei Li Guojun Chen Xingquan Xu Peter Abdou Qing Jiang Dongquan Shi Zhen Gu Department of Sports Medicine and Adult Reconstructive Surgery Drum Tower HospitalSchool of MedicineNanjing University321 Zhongshan RoadNanjing 210008JiangsuP.R.China Department of Bioengineering University of CaliforniaLos Angeles410 Westwood PlazaLos AngelesCA 90095USA California NanoSystems Institute University of CaliforniaLos Angeles570 Westwood PlazaLos AngelesCA 90095USA Jonsson Comprehensive Cancer Center University of CaliforniaLos Angeles8-684 Factor BuildingLos AngelesCA 90095USA Center for Minimally Invasive Therapeutics University of CaliforniaLos Angeles570 Westwood PlazaLos AngelesCA 90095USA

Articular cartilage is an important load-bearing tissue distributed on the surface of diarthrodial *** to its avascular,aneural and non-lymphatic features,cartilage has limited self-regenerative *** date,the utilization of biomaterials to aid in cartilage regeneration,especially through the use of injectable scaffolds,has attracted considerable *** materials,therapeutics and fabrication approaches have emerged with a focus on manipulating the cartilage microenvironment to induce the formation of cartilaginous structures that have similar properties to the native *** particular,the design and fabrication of injectable hydrogel-based scaffolds have advanced in recent years with the aim of enhancing its therapeutic efficacy and improving its ease of *** review summarizes recent progress in these efforts,including the structural improvement of scaffolds,network cross-linking techniques and strategies for controlled release,which present new opportunities for the development of injectable scaffolds for cartilage regeneration.

关键词： drug delivery tissue engineering injectable hydrogel cartilage regeneration

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Promoting lacunar bone regeneration with an injectable hydrogel adaptive to the microenvironment

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Bioactive Materials 2023年第3期21卷 403-421页

作者： Ao Zheng Xiao Wang Xianzhen Xin Lingjie Peng Tingshu Su Lingyan Cao Xinquan Jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and Materials639 Zhizaoju RoadShanghai200011China

injectable hydrogel is suitable for the repair of lacunar bone *** study fabricated an injectable,self-adaptive silk fibroin/mesoporous bioglass/sodium alginate(SMS)composite hydrogel *** controllable and adjustable physical and chemical properties,the SMS hydrogel could be easily optimized adaptively to different clinical *** SMS hydrogel effectively showed great injectability and shapeability,allowing defect filling with no ***,the SMS hydrogel displayed self-adaptability in mechanical reinforcement and degradation,responsive to the concentration of Ca2+and inflammatory-like pH value in the microenvi-ronment of bone deficiency,*** vitro biological studies indicated that SMS hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells by activation of the MAPK signaling *** SMS hydrogel also could improve migration and tube formation of human umbilical vein endothelial *** of the crosstalk between osteoblasts and macrophages confirmed that SMS hydrogel could regulate macrophage polarization from M1 to M2,which could create a specific favorable environment to induce new bone formation and ***,SMS hydrogel was proved to be antibacterial,especially for gram-negative ***,in vivo study indicated that SMS could be easily applied for maxillary sinus elevation,inducing sufficient new bone ***,it is convincing that SMS hydrogel could be potent in a simple,minimally invasive and efficient treatment for the repair of lacunar bone deficiency.

关键词： injectable hydrogel Oral and maxillofacial Silk fibroin Lacunar bone deficiency Bone regeneration

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Viscosity and degradation controlled injectable hydrogel for esophageal endoscopic submucosal dissection

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Bioactive Materials 2021年第11期6卷 1150-1162页

作者： Chaoqiang Fan Kaige Xu Yu Huang Shuang Liu Tongchuan Wang Wei Wang Weichao Hu Lu Liu Malcolm Xing Shiming Yang Department of Gastroenterology Xinqiao HospitalArmy Medical UniversityNO.183Xinqiao StreetShapingba DistrictChongqing City400037People’s Republic of China Department of Mechanical Engineering Biochemistry and Medical GeneticsUniversity of ManitobaWinnipeg MBR3T 2N2ManitobaCanada

Endoscopic submucosal dissection(ESD)is a common procedure to treat early and precancerous gastrointestinal *** submucosal injection,a liquid cushion is created to lift and separate the lesion and malignant part from the muscular layer where the formed indispensable space is convenient for endoscopic *** is a most common submucosal injection liquid,but the formed liquid pad lasts only a short time,and thus repeated injections increase the potential risk of adverse *** with high osmotic pressure and high viscosity are used as an alternate;however,with some drawbacks such as tissue damage,excessive injection resistance,and high ***,we reported a nature derived hydrogel of gelatin-oxidized alginate(G-OALG).Based on the rheological analysis and compare to commercial endoscopic mucosal resection(EMR)solution(0.25%hyaluronic acid,HA),a designed G-OALG hydrogel of desired concentration and composition showed higher performances in controllable gelation and injectability,higher viscosity and more stable *** G-OALG gel also showed lower propulsion resistance than 0.25%HA in the injection force assessment under standard endoscopic instruments,which eased the surgical *** addition,the G-OALG hydrogel showed good in vivo degradability *** comparing the results acquired via ESD to normal saline,the G-OALG shows great histocompatibility and excellent endoscopic injectability,and enables create a longer-lasting submucosal *** the features have been confirmed in the living both pig and rat *** G-OALG could be a promising submucosal injection agent for esophageal ESD.

关键词： injectable hydrogel Controllable gelation and viscosity Esophageal submucosal liquid cushion Early esophageal cancer Pig model

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Study on Preparation of Temperature-sensitive injectable hydrogel

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Chinese Journal of Biomedical Engineering(English Edition) 2010年第2期19卷 66-76页

作者： LIU Ling-xiu HU Guo-yin LIU Xin GU Han-qing Biomedical Engineering Department Tianjin Medical University Tianjin 300070 China Tianjin Institute of Urological Surgery Tianjin 300211 China

To get a sort of new scaffold material for soft tissue reconstruction,we have prepared XLHA-PNIPAAm and XLHA-MC injectable hydrogels through blending crosslinked HA(XLHA) and two temperature-sensitive materials differed in degradation poly(N-isopropylacrylamide)(PNIPAAm) and methylcellulose(MC),*** tested the injectablility,enzymatic biodegradability,temperature-sensitivity,structure cytotoxicity and hemolysis of the two injectable *** research has successfully obtained the preparation condition of XLHA-PNIPAAm injectable hydrogel,and verified that adding non-degradable material PNIPAAm can postpone the degradation of HA more effectively than degradable material *** prepared with 5 kGy dose radiation,MBAAm/NIPAAm(M/M)=0.015,monomer concentration=3% produced XLHA-PNIPAAm with slowest enzymatic *** results showed that temperature-sensitivity of the XLHA-PNIPAAm was more stable than that of *** composite hydrogels were qualified in cytotoxicity and hemolysis tests and the biocompatibility of XLHA-PNIPAAm hydrogel showed better than XLHA-MC hydrogel.

关键词： hyaluronan poly(N-isopropylacrylamide) methylcellulose injectable hydrogel tissue engineering

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An injectable conductive hydrogel restores electrical transmission at myocardial infarct site to preserve cardiac function and enhance repair

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生物活性材料(英文) 2023年第2期20卷 339-354页

作者： Linghong Zhang Tao Li Yan Yu Kun Shi Zhongwu Bei Yongjun Qian Zhiyong Qian State Key Laboratory of Biotherapy State Key Laboratory and Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengdu610041SichuanPR China Department of Cardiovascular Surgery West China HospitalSichuan UniversityChengdu610041SichuanPR China

Myocardial infarction(MI)leads to massive cardiomyocyte death and deposition of collagen *** fibrous tissue disrupts electrical signaling in the myocardium,leading to cardiac systolic and diastolic dysfunction,as well as *** hydrogels are a promising therapeutic strategy for ***,we prepared a highly water-soluble conductive material(GP)by grafting polypyrrole(PPy)onto non-conductive *** component was added to the gel system formed by the Schiff base reaction between oxidized xanthan gum(OXG)and gelatin to construct an injectable conductive *** prepared self-healing OGGP3(3 wt%GP)hydrogel had good biocompatibility,elastic modulus,and electrical conductivity that matched the natural *** prepared biomaterials were injected into the rat myocardial scar tissue 2 days after *** found that the cardiac function of the rats treated with OGGP3 was improved,making it more difficult to induce *** electrical resistivity of myocardial fibrous tissue was reduced,and the conduction velocity of myocardial tissue was *** analysis showed reduced infarct size,increased left ventricular wall thickness,increased vessel density,and decreased inflammatory response in the infarcted *** findings clearly demonstrate that the OGGP3 hydrogel attenuates ventricular remodeling and inhibits infarct dilation,thus showing its potential for the treatment of MI.

关键词： Myocardial infarction injectable hydrogel Conductivity Cardiac function

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injectable bioorthogonal hydrogel (BIOGEL) accelerates tissue regeneration in degenerated intervertebral discs

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Bioactive Materials 2023年第5期23卷 551-562页

作者： Jeffrey Luo Anjani Darai Thanapat Pongkulapa Brian Conley Letao Yang Inbo Han Ki-Bum Lee Department of Chemistry and Chemical Biology RutgersThe State University of New JerseyPiscatawayNJ08854USA Department of Neurosurgery CHA University School of MedicineCHA Bundang Medical Center59 Yaptap-roBundang-guSeongnam-siGyeonggi-do13496Republic of Korea

Intervertebral disc(IVD)degeneration is a leading cause of back pain and precursor to more severe conditions,including disc herniation and spinal *** traditional growth factor therapies(e.g.,TGFβ)are effective at transiently reversing degenerated disc by stimulation of matrix synthesis,it is increasingly accepted that bioscaffolds are required for sustained,complete IVD *** scaffolds(e.g.,metal/polymer composites,non-mammalian biopolymers)can be improved in one or more IVD regeneration demands:biodegradability,noninvasive injection,recapitulated healthy IVD biomechanics,predictable crosslinking,and matrix repair *** meet these demands,tetrazine-norbornene bioorthogonal ligation was combined with gelatin to create an injectable bioorthogonal hydrogel(BIOGEL).The liquid hydrogel precursors remain free-flowing across a wide range of temperatures and crosslink into a robust hydrogel after 5-10 min,allowing a human operator to easily inject the therapeutic constructs into degenerated ***,BIOGEL encapsulation of TGFβpotentiated histological repair(e.g.,tissue architecture and matrix synthesis)and functional recovery(e.g.,high water retention by promoting the matrix synthesis and reduced pain)in an in vivo rat IVD degeneration/nucleotomy *** BIOGEL procedure readily integrates into existing nucleotomy procedures,indicating that clinical adoption should proceed with minimal *** bioorthogonal crosslinking is essentially non-reactive towards biomolecules,our developed material platform can be extended to other payloads and degenerative injuries.

关键词： Bioorthogonal chemistry Growth factor injectable hydrogel Intervertebral disc degeneration Tissue engineering

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Ultrasound augmenting injectable chemotaxis hydrogel for articular cartilage repair in osteoarthritis

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Chinese Chemical Letters 2021年第5期32卷 1759-1764页

作者： Hui Liu Xi Xiang Jianbo Huang Bihui Zhu Liyun Wang Yuanjiao Tang Fangxue Du Ling Li Feng Yan Lang Ma Li Qiu Department of Ultrasound Laboratory of Ultrasound Imaging DrugWest China HospitalSichuan UniversityChengdu 610041China Department of Ultrasound The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

The increasing incidence of osteoarthritis(OA) seriously affects life quality,posing a huge socioeco nomic *** engineering technology has become a hot topic in articular cartilage repair as one of the key treatment methods to alleviate ***,one of the most commonly used scaffold materials,ca n provide a good extracellular matrix microenvironment fo r seed cells such as bone marrow mesenchymal stem cells(BMSCs),which can promote cartilage ***,the low homing rate of stem cells severely limits their role in promoting articular cartilage *** mal cell-derived factor-1α(SDF-1α) plays a crucial role in the activatio n,mobilization,homing,and migration of *** rein,a novel injectable chemotaxis hydrogel,composed of chitosan-based injectable hydrogel and embedding SDF-1α-loaded nanodroplets(PFP@NDs-PEG-SDF-1α) was designed and *** ultrasound was then used to augment the injectable chemotaxis hydrogel and promote the homing migration of BMSCs for OA cartilage *** effect of ultrasound augmenting injectable PFP@NDs-PEG-SDF-1α/hydrogel on the migration of BMSCs was verified in vitro and in vivo,which re markably promotes stem cell homing and the repair of cartilage in the OA ***,the treatment strategy of ultrasound augmenting injectable chemotaxis hydrogel has a bright potential for OA articular cartilage repair.

关键词： SDF-la injectable hydrogel Ultrasound Osteoarthritis Cartilage repair

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Polysaccharide based supramolecular injectable hydrogels for in situ treatment of bladder cancer

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Chinese Chemical Letters 2024年第1期35卷 259-263页

作者： Chang Zhang Jie Niu Jianqiu Li Hui Zhang Qilin Yu Yong Chen Yu Liu College of Chemistry State Key Laboratory of Elemento-Organic ChemistryNankai UniversityTianjin 300071China College of Life Sciences Key Laboratory of Molecular Microbiology and TechnologyNankai UniversityTianjin 300071China

Implantable system maximizes drug concentration and continuously releases drugs near the tumor,which is an effective tool to solve the difficult retention of chemotherapy drugs in bladder *** this work,a novel polysaccharide supramolecular injectable hydrogel(CCA hydrogels for short)is rapidly constructed by simply mixing cationic chitosan,anionic sulfobutyl etherβ-cyclodextrin(SBE-β-CD)and a trace amount of silver *** injected hydrogel reconstituted and regained its shape in less than 1 h,and it can still maintain the elasticity suitable for the human *** packaging the drug directly,the gel achieves a high concentration of doxorubicin,an anticancer *** MB49-luc cells as the model of bladder tumor for anti-tumor in vivo,the CCA-DOX gel has obvious inhibitory effect on bladder tumor,and its inhibitory effect is much greater than that of free ***,this self-healing injectable hydrogel has great potential for in situ treatment of bladder cancer.

关键词： Sulfobutylether-β-cyclodextrin Supramolecular chemistry Chitosan injectable hydrogel Bladder cancer Local chemotherapy

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