PDF(Pubmed)
Abstract：
Excessive exercise is an etiological factor of intervertebral disc degeneration (IVDD). Engineered extracellular vesicles (EVs) exhibit excellent therapeutic potential for disease-modifying treatments. Herein, we fabricate an exercise self-powered triboelectric-responsive microneedle (MN) assay with the sustainable release of optogenetically engineered EVs for IVDD repair. Mechanically, exercise promotes cytosolic DNA sensing-mediated inflammatory activation in senescent nucleus pulposus (NP) cells (the master cell population for IVD homeostasis maintenance), which accelerates IVDD. TREX1 serves as a crucial nuclease, and disassembly of TRAM1-TREX1 complex disrupts the subcellular localization of TREX1, triggering TREX1-dependent genomic DNA damage during NP cell senescence. Optogenetically engineered EVs deliver TRAM1 protein into senescent NP cells, which effectively reconstructs the elimination function of TREX1. Triboelectric nanogenerator (TENG) harvests mechanical energy and triggers the controllable release of engineered EVs. Notably, an optogenetically engineered EV-based targeting treatment strategy is used for the treatment of IVDD, showing promising clinical potential for the treatment of degeneration-associated disorders.
摘要：
过度运动是椎间盘退变（IVDD）的病因。工程化的细胞外囊泡(EV)对于疾病修饰治疗表现出优异的治疗潜力。在这里，我们制造了一种运动自供电的摩擦电响应微针（MN）测定法，可持续释放光基因工程EV用于IVDD修复。机械上,运动促进衰老髓核（NP）细胞（IVD稳态维持的主细胞群）的胞浆DNA传感介导的炎症激活，加速IVDD。TREX1作为一种关键的核酸酶,TRAM1-TREX1复合物的拆解会破坏TREX1的亚细胞定位，从而在NP细胞衰老过程中触发TREX1依赖性基因组DNA损伤。光基因工程电动汽车将TRAM1蛋白递送到衰老的NP细胞中，它有效地重建了TREX1的消除功能。摩擦电纳米发电机（TENG）收集机械能并触发工程电动汽车的可控释放。值得注意的是,基于光基因工程的EV靶向治疗策略用于IVDD的治疗，显示出治疗变性相关疾病的有希望的临床潜力。
