Brain Microenvironment Responsive and Pro‐Angiogenic Extracellular Vesicle‐Hydrogel for Promoting Neurobehavioral Recovery in Type 2 Diabetic Mice After Stroke

作者：Yixu Jiang, Ruiqi Wang, Cheng Wang, Yiyan Guo, Tongtong Xu, Zhijun Zhang, Guo‐Yuan Yang, He Xu, Yaohui Tang · 发表于：Advanced Healthcare Materials · 年份：2022 · DOI：10.1002/adhm.202201150 · 被引用次数：39 · 研究领域：Extracellular vesicles in disease、Neuroinflammation and Neurodegeneration Mechanisms、Nanoplatforms for cancer theranostics

Stroke patients with diabetes have worse neurological outcomes than non-diabetic stroke patients, and treatments beneficial for non-diabetic stroke patients are not necessarily effective for diabetic stroke patients. While stem cell-derived extracellular vesicles (EVs) show potential for treating stroke, the results remain unsatisfactory due to the lack of approaches for retaining and controlling EVs released into the brain. Herein, a glucose/reactive oxygen species dual-responsive hydrogel showing excellent injectability, biocompatibility, and self-healing capability is introduced as an EVs-loading vehicle and an intelligent EVs sustained releasing system in the brain. These EVs-hydrogels are developed via crosslinking of phenylboronic acid-modified hyaluronic acid and Poly vinyl alcohol, and fusion with neural stem cell-derived EVs. The results show EVs are stably incorporated into the hydrogels and can be controllably released in response to the brain microenvironment after stroke in type 2 diabetic mice. The EVs-hydrogels exert an excellent angiogenic effect, increasing the migration and tube formation of human umbilical vein endothelial cells. In addition, injection of EVs-hydrogels into the ischemic mouse brain enhances EVs retention and facilitates sustained release, promotes angiogenesis, and improves neurobehavioral recovery. These results suggest such a microenvironment responsive and sustained release EVs-hydrogel system offers a safe, and efficient therapy for dia...