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 oxidat...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.展开更多
基金the National Science Foundation of China(No.82272491,No.82072444)the Wuhan Science and Technology Bureau(2022020801020464)+2 种基金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).
文摘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.
