Extracellular vesicles (EVs) are heterogeneous membrane-like vesicles secreted by living cells that are involved in many physiological and pathological processes and act as intermediaries of intercellular communication and molecular transfer. Recent studies have shown that EVs from specific sources regulate tissue repair and regeneration by delivering proteins, lipids, and nucleic acids to target cells as signaling molecules. Nanotechnology breakthroughs have facilitated the development and exploration of engineered EVs for tissue repair. Enhancements through gene editing, surface modification, and content modification have further improved their therapeutic efficacy. This review summarizes the potential of EVs in tissue repair and regeneration, their mechanisms of action, and their research progress in regenerative medicine. This review highlights their design logic through typical examples and explores the development prospects of EVs in tissue repair. The aim of this review is to provide new insights into the design of EVs for tissue repair and regeneration applications, thereby expanding their use in regenerative medicine.

Esophageal squamous cell carcinoma (ESCC) carries a high risk of recurrence and metastasis and is associated with poor prognosis. Chemotherapy remains essential for ESCC treatment. Oxaliplatin (OXA), a third-generation platinum drug, offers advantages in cancer therapy; however, its lack of tumor targeting and high toxicity to normal cells limit clinical efficacy. To address this, we developed photothermal-assisted nanoparticles coated with N1-type neutrophil membranes engineered to express interleukin-21 (IL-21) on their surface and co-loaded with OXA and BMT-BBT (a photosensitizer) (OXA-BMT@ICVs) to enhance tumor killing. Results demonstrated effective uptake of OXA-BMT@ICVs by ESCC cells (KYSE-150) in vitro. This uptake induced immunogenic cell death (ICD) via activation of oxidative stress and mitochondrial dysfunction, further triggering the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway. In vivo studies revealed that, combined with photothermal therapy (PTT), OXA-BMT@ICVs accumulated within tumor tissue, enabling targeted release of OXA and BMT-BBT. The combined action of the cytokine IL-21 and the chemotherapeutic drug activated immune responses, promoting dendritic cell (DC) maturation and CD8+ T cell infiltration. This enhanced inflammatory responses and immune-mediated killing while activating the cGAS-STING pathway, thereby inducing ICD. The combination of OXA-BMT@ICVs and PTT significantly inhibited tumor cell proliferation, promoted apoptosis, and suppressed tumor growth in ESCC-bearing mice. This strategy activates potent immune responses, reduces systemic toxicity, exhibits good biocompatibility and safety, and represents a promising approach for ESCC clinical treatment.