Biomimetic Apoptotic Nanovesicles Derived from T Cells Target Neuroinflammation and Enhance Neural Regeneration via TGFBR2-Mediated Signaling for Spinal Cord Injury Repair

Spinal cord injury (SCI) remains a major clinical challenge because persistent neuroinflammation and limited intrinsic regeneration jointly impede functional recovery. Here, biomimetic apoptotic nanovesicles (Apo-nanovesicles) derived from early apoptotic Jurkat T cells are developed as a cell-free nanotherapeutic platform for SCI repair. The Apo-nanovesicles retain apoptosis-associated membrane cues, including phosphatidylserine, while exhibiting uniform nanoscale size, favorable colloidal stability, and good biocompatibility. In vitro, they are efficiently internalized by microglia, suppress pro-inflammatory activation, and promote a reparative phenotype. They also enhance neuronal differentiation of neural stem cells while reducing astroglial commitment. In a murine SCI model, Apo-nanovesicle treatment significantly improves locomotor recovery, attenuates glial scar formation, and establishes a regenerative lesion microenvironment. Transcriptomic profiling identifies TGF-β signaling as a major pathway associated with treatment response, and network analysis together with experimental validation reveals transforming growth factor-β receptor 2 (TGFBR2) as a central regulatory node. These findings indicate that Apo-nanovesicles promote SCI repair by coupling inflammatory resolution with neural regeneration through TGFBR2-mediated signaling. This work establishes apoptosis-mimetic nanovesicles as a promising biomimetic strategy for neuroregenerative therapy.