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This review provides a state\u2010of\u2010the\u2010art overview of Ti\u2010EV biology, critically evaluating current evidence from the liver, heart, adipose tissue, and skeletal muscle while identifying key challenges and future perspectives for clinical translation. We first categorize current isolation technologies by their validation status in the Ti\u2010EV context, and then survey organ\u2010specific functional profiles with emphasis on the functional shifts that accompany transitions between physiological and pathological states, as well as inter\u2010organ communication. Cross\u2010tissue comparison reveals conserved cargo classes, shared signaling pathways, and five recurrent regenerative mechanisms, including cell cycle regulation, metabolic reprogramming, microenvironment remodeling, angiogenesis, and programmed cell death control. These patterns point to three overarching principles: cargo composition encodes tissue identity, effector mechanisms are drawn from a constrained functional repertoire, and functional output is calibrated by tissue states. Engineering strategies for cargo reprogramming, controlled delivery, and targeted modification are discussed alongside bottlenecks in scalable production and regulatory compliance. This integrated framework positions Ti\u2010EVs as context\u2010dependent signaling systems and highlights single\u2010vesicle analysis, smart cargo editing, and personalized precision approaches as key directions for clinical translation.<\/jats:p>","DOI":"10.1002\/adma.74930","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:23:49Z","timestamp":1788852229000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leveraging Tissue\u2010Derived Extracellular Vesicles for Regenerative Medicine"],"prefix":"10.1002","author":[{"given":"Qi\u2010Lin","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology Fourth Military Medical University 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