Recent Advances in Exosome‐Based Nanodelivery Systems for Traumatic Brain Injury Treatment

ABSTRACT Traumatic brain injury (TBI) is a highly heterogeneous neurological condition with extremely high rates of mortality and disability. Currently, the clinical management of TBI relies primarily on palliative care, whereas complex secondary injury cascades limit the ability of traditional single‐target drugs to achieve consistent clinical benefits. Exosomes, as natural nanoscale extracellular vesicles, offer a highly promising innovative strategy for neuroprotection and repair in TBI due to their inherent ability to cross the blood–brain barrier (BBB), low immunogenicity, and potential for delivering multifunctional bioactive molecules. This review systematically summarizes the mechanisms of action of exosomes in TBI, including the regulation of neuroinflammation, inhibition of apoptosis, and promotion of angiogenesis and neural regeneration. We have thoroughly examined the specific biological characteristics, components, and translational potential of exosomes derived from various cell sources (such as mesenchymal stem cells and neural stem cells), and critically compared their advantages and disadvantages relative to conventional synthetic nanocarriers. To overcome the limitations of natural exosomes regarding in vivo delivery efficiency and stability, the article focuses on analyzing how engineering strategies (such as donor cell pretreatment, genetic engineering, exogenous loading, and surface modification) and macroscopic delivery strategies (such as local hydrogel/scaffold delivery) can achieve precision and controllability in exosome delivery. Given the challenges facing the clinical translation of exosomes, this review highlights the importance of standardized production processes, rigorous quality control, systematic pharmacokinetic/pharmacodynamic (PK/PD) studies, and clear regulatory pathways. We propose that future research should focus on the principle of minimal sufficient modification and develop precision treatment strategies stratified by TBI subtypes, integrating exosomes into multimodal combination therapies. The ultimate goal is to advance exosomes from the laboratory to standardized, regulated clinical applications, providing TBI patients with safe and effective new treatment options.