Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment  

作　　者：Yanpeng Cao Bei Chen Qixing Liu Yiyang Mao Yusheng He Xiaoren Liu Xin Zhao Yaowu Chen Xiying Li Yabei Li Liang Liu Chengwu Guo Shiyu Liu Fenghua Tan Hongbin Lu Jun Liu Can Chen 

机构地区：[1]Department of Limbs(Foot and Hand)Microsurgery,Chenzhou No.1 People’s Hospital,The First Clinical Medical College Affiliated to Southern Medical University,Chenzhou,Hunan,China [2]Department of Orthopedics,Xiangya Hospital,Central South University,Changsha,Hunan,China [3]National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha,Hunan,China [4]Department of Sports Medicine,Xiangya Hospital,Central South University Changsha,Hunan,China [5]Key Laboratory of Organ Injury,Aging and Regenerative Medicine of Hunan Province,Changsha,Hunan,China

出　　处：《Bioactive Materials》2024年第12期32-51,共20页生物活性材料（英文）

基　　金：financially supported through grants from the National Natural Science Foundation of China(Grant No.82272497);Hunan Provincial Natural Science Foundation(Grant Nos.2021JJ20093,2022JJ30001,2023JJ40090);the Hunan Provincial Health Commission Scientific Research Projects(Grant No.202204075237).

摘　　要：Due to overactive inflammation and hindered angiogenesis,self-healing of diabetic wounds(DW)remains challenging in the clinic.Platelet-derived exosomes(PLT-Exos),a novel exosome capable of anti-inflammation and pro-angiogenesis,show great potential in DW treatment.However,previous administration of exosomes into skin wounds is topical daub or intradermal injection,which cannot intradermally deliver PLT-Exos into the dermis layer,thus impeding its long-term efficacy in anti-inflammation and pro-angiogenesis.Herein,a dissolvable microneedle-based wound dressing(PLT-Exos@ADMMA-MN)was developed for transdermal and long-term delivery of PLT-Exos.Firstly,a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel(ADMMA-GEL),showing physiochemical tailorability,fast-gelling performance,excellent biocompatibility,and pro-angiogenic capacities,was synthesized as a base material of our dressing.For endowing the dressing with anti-inflammation and pro-angiogenesis,PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro experiments.Then,in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and pro-angiogenesis.Lastly,in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization,thus proving a low-inflammatory and pro-angiogenic microenvironment for DW healing.Collectively,this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

关 键 词：Acellular dermal matrix Diabetic wound EXOSOMES MICRONEEDLE Transdermal delivery 

分 类 号：R587.1[医药卫生—内分泌]