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Glucose-responsive,antioxidative HA-PBA-FA/EN106 hydrogel enhanced diabetic wound healing through modulation of FEM1b-FNIP1 axis and promoting angiogenesis

查看全文 作　　者：Wenqian [1,2]Zhang;Kangkang [1,2]Zha;Yuan [1,2]Xiong;Weixian [1,2]Hu;Lang [1,2]Chen;Ze [1,2]Lin;Chenyan [1,2]Yu;Wu [1,2]Zhou;Faqi [1,2]Cao;Hankun [3,4,5]Hu;Bobin [1,2]Mi;Guohui [1,2]Liu 高影响力作者 机构地区：[1]Department of Orthopaedics,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China;[2]Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration,Wuhan,430022,China;[3]Department of Pharmacy,Zhongnan Hospital of Wuhan University,School of Pharmaceutical Sciences,Wuhan University,Wuhan 430071,China;[4]Hubei Micro-explore Innovative Pharmaceutical Research Co,Ltd,Wuhan,Hubei,430071,PR China;[5]Suzhou Organ-on-a-Chip System Science and Technology Co,Ltd,Suzhou,Jiangsu,215000,PR China高影响力机构 出　　处：《Bioactive Materials》索引2023年第12期,共17页高影响力期刊 基　　金：the National Science Foundation of China(No.82272491,No.82072444);the Wuhan Science and Technology Bureau(2022020801020464);the Department of Science and Technology of Hubei Province(No.2021CFB425);Chinese Pharmaceutical Association Hospital Phamacy department(No.CPA-Z05-ZC-2022-002);Grants from Hubei Province Unveiling Science and Technology Projects(No.2022-35). 摘　　要：The diabetic wounds remain to be unsettled clinically,with chronic wounds characterized by drug-resistant bacterial infections,compromised angiogenesis and oxidative damage to the microenvironment.To ameliorate oxidative stress and applying antioxidant treatment in the wound site,we explore the function of folliculininteracting protein 1(FNIP1),a mitochondrial gatekeeper protein works to alter mitochondrial morphology,reduce oxidative phosphorylation and protect cells from unwarranted ROS accumulation.And our in vitro experiments showed the effects of FNIP1 in ameliorating oxidative stress and rescued impaired angiogenesis of HUVECs in high glucose environment.To realize the drug delivery and local regulation of FNIP1 in diabetic wound sites,a novel designed glucose-responsive HA-PBA-FA/EN106 hydrogel is introduced for improving diabetic wound healing.Due to the dynamic phenylboronate ester structure with a phenylboronic acid group between hyaluronic acid(HA)and phenylboronic acid(PBA),the hydrogel is able to realize a glucose-responsive release of drugs.Fulvic acid(FA)is added in the hydrogel,which not only severs as crosslinking agent but also provides antibacterial and anti-inflammatory abilities.Moreover,the release of FEM1b-FNIP1 axis inhibitor EN106 ameliorated oxidative stress and stimulated angiogenesis through FEM1b-FNIP1 axis regulation.These in vivo and in vitro results demonstrated that accelerated diabetic wounds repair with the use of the HA-PBA-FA/EN106 hydrogel,which may provide a promising strategy for chronic diabetic wound repair. 关 键 词：FNIP1 Wound healing HYDROGEL Antioxidant Glucose-responsive
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