Self-powered triboelectric-responsive microneedles with controllable release of optogenetically engineered extracellular vesicles for intervertebral disc degeneration repair.
Weifeng ZhangXuan QinGaocai LiXingyu ZhouHongyang LiDi WuYu SongKangcheng ZhaoKun WangXiaobo FengLei TanBingjin WangXuhui SunZhen WenCao YangPublished in: Nature communications (2024)
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.
Keyphrases
- dna damage
- induced apoptosis
- high intensity
- physical activity
- single cell
- cancer therapy
- cell therapy
- cell cycle arrest
- oxidative stress
- stem cells
- high throughput
- risk assessment
- body mass index
- cell free
- mesenchymal stem cells
- transcription factor
- copy number
- dna repair
- smoking cessation
- bone marrow
- weight gain
- binding protein
- stress induced