机构：[1]Orthopedics Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.四川大学华西医院[2]Trauma Medical Center, Department of Orthopedics Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.四川大学华西医院[3]Head & Neck Oncology Ward, Cancer Center, West China Hospital, Cancer Center, Sichuan University, Chengdu 610041, P. R. China.四川大学华西医院[4]Spine lab, Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.浙江大学医学院附属第一医院[5]Department of Orthopedic Trauma, The First People's Hospital of Kunshan affiliated with Jiangsu University, Suzhou, Jiangsu 215300, P. R. China.[6]Department of Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, P. R. China.[7]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, P. R. China.
Critical peripheral nerve deficiencies present as one of the most formidable conundrums in the realm of clinical medicine, frequently culminating in structural degradation and derangement of the neuromuscular apparatus. Engineered extracellular vesicles (EVs) exhibit the potential to ameliorate nerve impairments. However, the advent of Wallerian degeneration (WD), an inexorable phenomenon that ensues post peripheral nerve injury, serves as an insurmountable impediment to the direct therapeutic efficacy of EVs. In this investigation, we have fashioned a dynamic network for the conveyance of PTEN-induced kinase 1 (PINK1) mRNA (E-EV-P@HPCEP) using an adaptive hydrogel with reactive oxygen species (ROS)/Ca2+ responsive ability as the vehicle, bearing dual-targeted, engineered EVs. This intricate system is to precisely deliver PINK1 to senescent Schwann cells (SCs) while concurrently orchestrating a transformation in the inflammatory-senescent milieu following injury, thereby stymying the progression of WD in peripheral nerve fibers through the stimulation of autophagy within the mitochondria of the injured cells and the maintenance of mitochondrial mass equilibrium. WD, conventionally regarded as an inexorable process, E-EV-P@HPCEP achieved functionalized EV targeting, orchestrating a dual-response dynamic release mechanism via boronate ester bonds and calcium chelation, effectuating an enhancement in the inflammatory-senescent microenvironment, which expedites the therapeutic management of nerve deficiencies and augments the overall reparative outcome.
基金：
Natural Science Foundation of Sichuan (2024NSFSC1507, 2023NSFSC1835), the Tibet Autonomous Region cofunded project (XZ202301ZY0046G),the Post-Doctor Research Project of West China Hospital,Sichuan University (2023HXBH106), and the China Postdoctoral Science Foundation (2023M742468, 2023M732467,
2023TQ0224), and the Fund of the High-quality Development of Guang’an People’s Hospital (21FZ014).
第一作者机构：[1]Orthopedics Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.[2]Trauma Medical Center, Department of Orthopedics Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.
共同第一作者：
通讯作者：
通讯机构：[1]Orthopedics Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.[2]Trauma Medical Center, Department of Orthopedics Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.
材料科学