Abstract：
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.
摘要：
严重的周围神经缺陷是临床医学领域中最棘手的难题之一，经常导致神经肌肉装置的结构退化和紊乱。工程化的细胞外囊泡（EV）具有改善神经损伤的潜力。然而,Wallerian变性（WD）的出现，周围神经损伤后产生的一种不可阻挡的现象，对电动汽车的直接治疗效果是一个不可逾越的障碍。在这次调查中,我们使用具有活性氧（ROS）/Ca2响应能力的自适应水凝胶作为载体，构建了PTEN诱导的激酶1（PINK1）mRNA（E-EV-P@HPCEP）的动态网络，轴承双目标，工程电动汽车。这个复杂的系统是精确地将PINK1递送到衰老的施万细胞（SC），同时在损伤后的炎症衰老环境中协调转化，从而通过刺激受损细胞线粒体内的自噬和维持线粒体质量平衡来阻碍外周神经纤维中WD的进展。WD,通常被认为是一个不可阻挡的过程，E-EV-P@HPCEP实现了功能化EV靶向，通过硼酸酯键和钙螯合协调双响应动态释放机制，实现炎症衰老微环境的增强，这加快了神经缺陷的治疗管理，并增加了整体的修复结果。
