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

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.