Exosome-Based Diagnostics and Cell-Free Therapeutics for Traumatic Brain Injury: From Mechanisms to Bedside

Abstract: Traumatic brain injury (TBI) is one of the leading neurological disorders worldwide. The complexity of its pathological mechanisms and substantial interindividual variability pose considerable challenges to conventional diagnostic and therapeutic approaches. Exosomes, a subtype of extracellular vesicles, have attracted growing interest due to their excellent biocompatibility and ability to cross the blood–brain barrier, demonstrating considerable potential in TBI diagnosis and treatment. This review focuses on the application of exosomes in the field of TBI, clarifying the pathophysiological mechanisms by which exosomes regulate inflammation, neuronal repair, vascular changes and cognitive function after TBI, and discussing their value as novel biomarkers in the early diagnosis and prognosis assessment of TBI. Subsequently, we summarize the application of exosome tissue engineering in TBI, comb through the preclinical translational basis of exosomes, and analyze the current challenges including standardization of isolation procedures, safety and long-term efficacy. In summary, exosomes provide a novel paradigm for cell-free therapy and precision diagnosis of TBI, and further addressing translational bottlenecks will enable them to exert greater advantages. Keywords: exosome, traumatic brain injury, biomarker, tissue engineering, cell-free therapy