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Antioxidant biocompatible composite collagen dressing for diabetic wound healing in rat model

Regenerative Biomaterials 2021年第2期8卷 74-84页

作者： Bei Qian Jialun Li Ke Guo Nengqiang Guo Aimei Zhong Jie Yang Jiecong Wang Peng Xiao Jiaming Sun Lingyun Xiong Department of Plastic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and Technology1277 Jiefang AvenueWuhan 430022China Wuhan Clinical Research Center for Superficial Organ Reconstruction Wuhan 430022China

Associated with persistent oxidative stress,altered inflammatory responses,poor angiogenesis and epithelization,wound healing in diabetic patients is impaired.N-acetylcysteine(NAC)is reported to resist excess reactive oxygen species(ROS)production,prompt angiogenesis and maturation of the epidermis.Studies have revealed that graphene oxide(GO)can regulate cellular behavior and form cross-links with naturally biodegradable polymers such as collagen(COL)to construct composite scaffolds.Here,we reported a COL-based implantable scaffold containing a mixture of GO capable of the sustained delivery of NAC to evaluate the wound healing in diabetic rats.The morphological,physical characteristics,biocompatibility and NAC release profile of the GO-COL-NAC(GCN)scaffold were evaluated in vitro.wound healing studies were performed on a 20mm dorsal full-skin defect of streptozotocin(STZ)-induced diabetic rats.The injured skin tissue was removed at the 18th day post-surgery for histological analysis and determination of glutathione peroxidase(GPx),catalase(CAT)and superoxide dismutase(SOD)activity.In diabetic rats,we confirmed that the GCN scaffold presented a beneficial effect in enhancing the wound healing process.Additionally,due to the sustained release of NAC,the scaffold may potentially induce the antioxidant defense system,upregulating the expression levels of the antioxidant enzymes in the wound tissue.The findings revealed that the antioxidant biocompatible composite collagen dressing could not only deliver NAC in situ for ROS inhibition but also promote the wound healing process.This scaffold with valuable therapy potential might enrich the approaches for surgeon in diabetic wound treatment in the future.

关键词： collagen graphene oxide N-acetylcysteine sustained release diabetic wound healing

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An intrinsically bioactive hydrogel with on-demand drug release behaviors for diabetic wound healing

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Bioactive Materials 2021年第12期6卷 4592-4606页

作者： Bin Hu Mingzhu Gao Kofi Oti Boakye-Yiadom William Ho Wei Yu Xiaoyang Xu Xue-Qing Zhang Engineering Research Center of Cell&Therapeutic Antibody Ministry of Educationand School of PharmacyShanghai Jiao Tong University800 Dongchuan RoadShanghai200240PR China Department of Chemical and Materials Engineering New Jersey Institute of TechnologyNewarkNJ07102USA

Prolonged,intense inflammation and excessive oxidative stress hinder diabetic wounds from healing normally,leading to disorders downstream including the postponement of re-epithelialization and extracellular matrix(ECM)formation.Herein,we report a hyaluronic acid(HA)and chitosan based hydrogel(OHA-CMC)with inherent antibacterial and hemostatic activities fabricated via Schiff base reaction.By encapsulating nanotechnologically-modified curcumin(CNP)and epidermal growth factor(EGF)into the hydrogel,OHA-CMC/CNP/EGF exhibited extraordinary antioxidant,anti-inflammatory,and migration-promoting effects in vitro.Meanwhile,OHA-CMC/CNP/EGF presented on-demand drug release in synchrony with the phases of the wound healing process.Specifically,curcumin was rapidly and constantly released to alleviate inflammation and oxidative stress in the early phase of wound healing,while a more gradual and sustained release of EGF supported late proliferation and ECM remodeling.In a diabetic full-thickness skin defect model,OHA-CMC/CNP/EGF dramatically improved wound healing with ideal re-epithelialization,granulation tissue formation,and skin appendage regeneration,highlighting the enormous therapeutic potential this biomaterial holds as a diabetic wound dressing.

关键词： Bioactive hydrogel Drug delivery Anti-Inflammation Antioxidant diabetic wound healing

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Cobalt-based metal-organic framework as a dual cooperative controllable release system for accelerating diabetic wound healing

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Nano Research 2020年第8期13卷 2268-2279页

作者： Jiankai Li Fang Lv Jinxiu Li Yuxin Li Jingduo Gao Jian Luo Feng Xue Qinfei Ke He Xu College of Chemical and Materials Sciences Shanghai Normal UniversityNo.100 Guilin RoadShanghai200234China Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Science and School of Life ScienceEast China Normal UniversityShanghai200241China School of Materials Science and Engineering Shanghai Institute of TechnologyNo.120 Caobao RoadShanghai200235China Southern Medical University Affiliated Fengxian Hospital 6600 Nanfeng RoadShanghai201499China

Nano Research volume 13,pages2268–2279(2020)Cite this article 131 Accesses 1 Altmetric Metrics details Abstract Insufficient angiogenesis in the chronic wound of the diabetic is one of the most important causes that making the wound unable to heal itself.In this work,a cobalt-based metal–organic framework(ZIF-67)was introduced as a carrier for loading a pro-angiogenic small molecular drug(dimethyloxalylglycine,DMOG).To achieve a long-term angiogenic therapy on the diabetic wound beds,a dual cooperative controllable release system has been designed by incorporating the drug-loaded ZIF-67 nanoparticles into the micro-patterned PLLA/Gelatin nanofibrous scaffolds.The results showed that DMOG was incorporated into ZIF-67 with a high loading ratio(359.12 mg/g),and the drug-loaded ZIF-67 nanoparticles were well embedded in the circular patterned scaffold.Notably,the DMOG as well as Co ions could continuously release from the scaffold for more than 15 days.The in vitro studies showed that the released Co ions and DMOG from the micropatterned nanofibrous scaffolds could synergistically promote the proliferation,migration and tube formation of the human umbilical vein endothelial cells(HUVECs)by inducing a hypoxia response and upregulating the expression of angiogenesis-related genes such as HIF-1α,VEGF and e-NOS.Furthermore,the in vivo results demonstrated that the composite scaffolds could significantly enhance angiogenesis,collagen deposition and eliminate inflammation in the diabetes wounds.These results indicate that the cobalt-based metal–organic framework as a dual cooperative controllable release system provides a new strategy for enhancing angiogenesis and promoting diabetic wound healing.

关键词： metal-organic framework cobalt ion drug delivery angiogenesis diabetic wound healing

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Electrospinning:An emerging technology to construct polymer-based nanofibrous scaffolds for diabetic wound healing

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Frontiers of Materials Science 2021年第1期15卷 10-35页

作者： Atta ur Rehman KHAN Yosry MORSI Tonghe ZHU Aftab AHMAD Xianrui XIE Fan YU Xiumei MO State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of ChemistryChemical Engineering and BiotechnologyDonghua UniversityShanghai 201620China Faculty of Engineering and Industrial Sciences Swinburne University of TechnologyBoroondaraVIC 3122Australia Multidisciplinary Center for Advanced Materials of Shanghai University of Engineering Science College of Chemistry and Chemical EngineeringShanghai University of Engineering ScienceShanghai 201620China Department of Bioscience cOMSATS Institute of Information TechnologyPakistan

A chronic wound in diabetic patients is a major public health concern withsocioeconomic and clinical manifestations.The underlying medical condition of diabeticpatients deteriorates the wound through physiological,metabolic,molecular,and cellularpathologies.Consequently,a wound enters a vicious pathological inflammatory cycle.Many therapeutic approaches are in practice to manage diabetic wounds hence ensuringthe regeneration process.Polymer-based biomaterials have come up with hightherapeutic promises.Many efforts have been devoted,over the years,to build aneffective wound healing material using polymers.The electrospinning technique,although not new,has turned out to be one of the most effective strategies in buildingwound healing biomaterials due to the special structural advantages of electrospunnanofibers over the other formulations.In this review,careful integration of allelectrospinning approaches has been presented which will not only give an insight intothe current updates but also be helpful in the development of new therapeutic materialconsidering pathophysiological conditions of a diabetic wound.

关键词： diabetic wound healing inflammation polymers bioactive substances hydrogel electrospinning nanofibers

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Bioactive glass promotes the barrier functional behaviors of keratinocytes and improves the Re-epithelialization in wound healing in diabetic rats

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Bioactive Materials 2021年第10期6卷 3496-3506页

作者： Fengling Tang Junliang Li Weihan Xie Yunfei Mo Lu Ouyang Fujian Zhao Xiaoling Fu Xiaofeng Chen Department of Biomedical Engineering School of Materials Science and EngineeringSouth China University of TechnologyGuangzhou 510641PR China National Engineering Research Center for Tissue Restoration and Reconstruction Guangzhou 510006PR China Key Laboratory of Biomedical Engineering of Guangdong Province and Innovation Center for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhou 510006PR China Stomatological Hospital Southern Medical UniversityGuangzhou 510280PR China

Upon skin injury,re-epithelialization must be triggered promptly to restore the integrity and barrier function of the epidermis.However,this process is often delayed or interrupted in chronic wounds like diabetic foot ulcers.Considering that BG particles can activate multiple genes in various cells,herein,we hypothesized that bioactive glass(BG)might be able to modulate the barrier functional behaviors of keratinocytes.By measuring the transepithelial electrical resistance(TEER)and the paracellular tracer flux,we found the 58S-BG extracts substantially enhanced the barrier function of keratinocyte monolayers.The BG extracts might exert such effects by promoting the keratinocyte differentiation and the formation of tight junctions,as evidenced by the increased expression of critical differentiation markers(K10 and involucrin)and TJ protein claudin-1,as well as the altered subcellular location of four major TJ proteins(claudin-1,occludin,JAM-A,and ZO-1).Besides,the cell scratch assay showed that BG extracts induced the collective migration of keratinocytes,though they did not accelerate the migration rate compared to the control.The in vivo study using a diabetic rat wound model demonstrated that the BG extracts accelerated the process of re-epithelialization,stimulated keratinocyte differentiation,and promoted the formation of tight junctions in the newly regenerated epidermis.Our findings revealed the crucial effects of BGs on keratinocytes and highlighted its potential application for chronic wound healing by restoring the barrier function of the wounded skin effectively.

关键词： Bioactive glass Keratinocyte Barrier function diabetic wound healing

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Topically delivered i PSs accelerate diabetic wound healing via heme oxygenase-1

Topically delivered i PSs accelerate diabetic wound healing ...

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中国生理学会第24届全国会员代表大会暨生理学学术大会

作者：陈思锋 Xinhong Wang Ming Xu Ning Li Meng Xiang Dan Meng Chao Lu Jing Quan Peng Lu Sun Ning Rui Wang Alex F.Chen Department of Physiology and Pathophysiology Fudan University Shanghai Medical College Department of Biology Lakehead UniversityThunder BayOntarioCanada P7B 5E1 Department of Surgery University of Pittsburgh School of MedicinePittsburghPAUSA

Poor blood and stem/progenitor cell supplies underlie wound healing impairment in diabetic patients.Induced pluripotent stem cells（i PSs）have great therapeutic potential;however,it is not clear whether i PSs can promote wound healing are unknown.Directly application of i PSs on a body or wound surface has not yet been reported.This study aimed to demonstrate the effect and associated mechanisms of topically applied i PSs on wound healing in diabetic mice.In streptozocin-induced type 1 diabetic mice,we found that i PSs accelerated skin wound healing,and promoted re-epithelialization and angiogenesis,while increasing expression of proangiogenic factors and receptors in the diabetic wound.The applied cells survived in the lesion and many differentiated into vascular endothelial cells.Knockdown of heme oxygenase-1（HO-1）in i PSs blocked these beneficial effects and the differentiation of i PSs.The mice did not develop teratoma after i PS treatment over a follow-up of 3 months.Our results show that i PSs accelerate diabetic wound healing through a proangiogenic effect in a HO-1–dependent manner.Topical delivery of i PSs may be a novel approach to achieve i PS therapy while circumventing the major shortcomings of existing i PS administration routes.

关键词： i PSs diabetic wound healing heme oxygenase-1

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Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles

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Bioactive Materials 2023年第9期27卷 257-270页

作者： Ziqiang Chu Qilin Huang Kui Ma Xi Liu Wenhua Zhang Shengnan Cui Qian Wei Huanhuan Gao Wenzhi Hu Zihao Wang Sheng Meng Lige Tian Haihong Li Xiaobing Fu Cuiping Zhang Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital28 Fuxing RoadBeijing100853PR China Chinese PLA Medical School 28 Fuxing RoadBeijing100853PR China College of Graduate Tianjin Medical UniversityTianjin300070PR China Research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU05151 Fucheng RoadBeijing100048PR China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and RegenerationChinese PLA Hospital and PLA Medical College51 Fucheng RoadBeijing100048PR China Department of Dermatology China Academy of Chinese Medical ScienceXiyuan HospitalBeijing100091PR China Department of wound Repair Institute of Wound Repair and Regeneration MedicineSouthern University of Science and Technology HospitalSouthern University of Science and Technology School of MedicineShenzhen518055PR China

Neutrophil extracellular traps(NETs)have been considered a significant unfavorable factor for wound healing in diabetes,but the mechanisms remain unclear.The therapeutic application of small extracellular vesicles(sEVs)derived from mesenchymal stem cells(MSCs)has received considerable attention for their properties.Hypoxic preconditioning is reported to enhance the therapeutic potential of MSC-derived sEVs in regenerative medicine.Therefore,the aim of this study is to illustrate the detailed mechanism of NETs in impairment of diabetic wound healing and develop a promising NET-targeting treatment based on hypoxic pretreated MSC-derived sEVs(Hypo-sEVs).Excessive NETs were found in diabetic wounds and in high glucose(HG)-induced neutrophils.Further research showed that high concentration of NETs impaired the function of fibroblasts through activating endoplasmic reticulum(ER)stress.Hypo-sEVs efficiently promoted diabetic wound healing and reduced the excessive NET formation by transferring miR-17-5p.Bioinformatic analysis and RNA interference experiment revealed that miR-17-5p in Hypo-sEVs obstructed the NET formation by targeting TLR4/ROS/MAPK pathway.Additionally,miR-17-5p overexpression decreased NET formation and overcame NET-induced impairment in fibroblasts,similar to the effects of Hypo-sEVs.Overall,we identify a previously unrecognized NET-related mechanism in diabetic wounds and provide a promising NET-targeting strategy for wound treatment.

关键词： diabetic wound healing Neutrophil extracellular traps Small extracellular vesicles Hypoxia Endoplasmic reticulum stress

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Regenerative antibacterial hydrogels from medicinal molecule for diabetic wound repair

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Bioactive Materials 2023年第7期25卷 541-554页

作者： Chunxiao Chai Pengfei Zhang Lin Ma Qi Fan Zhicheng Liu Xiang Cheng Yunpeng Zhao Weiwei Li Jingcheng Hao Key Laboratory of Colloid and Interface Chemistry(Shandong University) Ministry of EducationJinan250100PR China Department of Orthopaedic Surgery Qilu HospitalCheeloo College of MedicineShandong UniversityJinan250012PR China Cheeloo College of Medicine Shandong UniversityJinan250012PR China Department of Pathology Qilu HospitalCheeloo College of MedicineShandong UniversityJinan250012PR China Laboratory of Basic Medical Sciences Qilu HospitalCheeloo College of MedicineShandong UniversityJinan250012PR China

Hydrogel products for chronic diabetic wounds,a serious and prevalent complication of diabetes,show limited effects on disability and remain nonspecific.Thus,improvements in the usage of pharmaceutical molecule in the hydrogels are highly desirable to increase the therapeutic effect of hydrogels.In this study,thioctic acid(a common medicine molecule in diabetes treatment)is used for preparing regenerative antibacterial hydrogels(RAH)which contains in situ synthesized silver nanoparticles(AgNPs).The RAH shows regenerative,self-healing and injectable ability,because of the reversible hydrogen and coordination bonds.With good regenerative capacity,RAH can be stored as powder to avoid the water loss and facilitate storage availability.Owing to the antioxidant properties of thioctic acid,the RAH can decrease the oxidative damage and retain cell proliferation efficiency.Due to the in situ synthesized AgNPs,the RAH also exhibits extraordinary antimicrobial capacities against MDR bacteria.All of these superiorities enable RAH to be a promising therapy for chronic diabetic wounds.

关键词： diabetic wound healing Antibacterial hydrogel Thioctic acid Antioxidant Regeneration

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Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles:Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus

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Bioactive Materials 2023年第9期27卷 409-428页

作者： Qing-Song Deng Yuan Gao Bi-Yu Rui Xu-Ran Li Po-Lin Liu Zi-Yin Han Zhan-Ying Wei Chang-Ru Zhang Fei Wang Helen Dawes Tong-He Zhu Shi-Cong Tao Shang-Chun Guo Department of Orthopedic Surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine600 Yishan RoadShanghai200233China School of Medicine Shanghai Jiao Tong University227 South Chongqing RoadShanghai200025China Institute of Microsurgery on Extremities Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine600 Yishan RoadShanghai200233China Department of Rheumatology The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical UniversityNo.29XinglongxiangTianning DistrictChangzhou213000China Shanghai Clinical Research Centre of Bone Diseases Department of Osteoporosis and Bone DiseasesShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200233China Shanghai Key Laboratory of Orthopedic Implants Department of Orthopedic SurgeryShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineNo.639 Zhizaoju RoadShanghai200011China Clinical and Translational Research Center for 3D Printing Technology Medical 3D Printing Innovation Research CenterShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai200125China Department of Orthopedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin Second RoadShanghai200025China Faculty of Health and Life Science Oxford Brookes UniversityHeadington RoadOxfordOX30BPUK NIHR Oxford Health Biomedical Research Centre OxfordOX37JXUK College of Medicine and Health St Lukes CampusUniversity of ExeterHeavitree RoadExeterEX12LUUK School of Chemistry and Chemical Engineering Shanghai Engineering Research Center of Pharmaceutical Intelligent EquipmentShanghai Frontiers Science Research Center for Druggability of Cardiovascular Non-Coding RNAInstitute for Frontier Medical TechnologyShanghai University of

diabetic wound healing has become a serious healthcare challenge.The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction,resulting in chronic inflammation,abnormal vascular function,and tissue necrosis.To solve these issues,we developed a double-network hydrogel,constructed with pluronic F127 diacrylate(F127DA)and hyaluronic acid methacrylate(HAMA),and enhanced by SS31-loaded mesoporous polydopamine nanoparticles(MPDA NPs).As components,SS31,a mitochondria-targeted peptide,maintains mitochondrial function,reduces mitochondrial reactive oxygen species(ROS)and thus regulates macrophage polarization,as well as promoting cell proliferation and migration,while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation,but also control release of SS31 in response to ROS.This F127DA/HAMA-MPDA@SS31(FH-M@S)hydrogel has characteristics of adhesion,superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31(M@S)NPs.In addition,in a diabetic rat full thickness skin defect model,the FH-M@S hydrogel promoted macrophage M2 polarization,collagen deposition,neovascularization and wound healing.Therefore,the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration.

关键词： Mesoporous polydopamine nanoparticles(MPDA NPs) SS31 Photothermal antibacterial Mitochondrial function maintenance diabetic wound healing

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An injectable bioactive dressing based on platelet-rich plasma and nanoclay:Sustained release of deferoxamine to accelerate chronic wound healing

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4318-4336页

作者： Jiao Zhang Qian Luo Qian Hu Tiantian Zhang Jingyu Shi Li Kong Dehao Fu Conglian Yang Zhiping Zhang Tongji School of Pharmacy Huazhong University of Science and TechnologyWuhan 430030China Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology Wuhan 430030China Department of Orthopaedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China National Engineering Research Center for Nanomedicine Huazhong University of Science and TechnologyWuhan 430030China Hubei Engineering Research Center for Novel Drug Delivery System Huazhong University of Science and TechnologyWuhan 430030China

Delayed diabetic wound healing has placed an enormous burden on society.The key factors limiting wound healing include unresolved inflammation and impaired angiogenesis.Platelet-rich plasma(PRP)gel,a popular biomaterial in the field of regeneration,has limited applications due to its non-injectable properties and rapid release and degradation of growth factors.Here,we prepared an injectable hydrogel(DPLG)based on PRP and laponite by a simple one-step mixing method.Taking advantages of the non-covalent interactions,DPLG could overcome the limitations of PRP gels,which is injectable to fill irregular injures and could serve as a local drug reservoir to achieve the sustained release of growth factors in PRP and deferoxamine(an angiogenesis promoter).DPLG has an excellent ability in accelerating wound healing by promoting macrophage polarization and angiogenesis in a full-thickness skin defect model in typeⅠdiabetic rats and normal rats.Taken together,this study may provide the ingenious and simple bioactive wound dressing with a superior ability to promote wound healing.

关键词： Injectable hydrogels diabetic wound healing Platelet-rich plasma Laponite Deferoxamine Angiogenesis Macrophage polarization

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