Mesenchymal Stem Cell-derived exosomes loaded Alitretinoin for TBI repair treatment

Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity worldwide. Current clinical treatments often target singular pathological processes, resulting in suboptimal outcomes due to a lack of comprehensive neuroprotective effects. To address this critical gap, we have developed an innovative therapeutic approach utilizing mesenchymal stromal cell (MSC)-derived exosome (Mexo)-coated albumin nanospheres loaded with Alitretinoin (Ali-NPs@Mexo). This novel design aims to enhance neural repair mechanisms, offering a multifaceted approach to neuroprotection and recovery in TBI patients. Our in vitro and in vivo experiments demonstrated that Ali-NPs@Mexo effectively modulates the TBI immuno-microenvironment by attenuating oxidative stress and neuroinflammatory responses. Treatment with Ali-NPs@Mexo was also found to reduce the abnormal activation of astrocytes, which contribute to glial scar formation that hinders neuronal repair. Furthermore, this nanomedicine promoted the proliferation and repair of oligodendrocytes, neural stem cells, and neurons. These findings underscore the potential of Ali-NPs@Mexo as a robust therapeutic strategy for TBI, combining targeted delivery with comprehensive anti-inflammatory, neuroprotective, and reparative effects. The innovative use of MSC-derived exosome-coated nanoparticles ensures enhanced brain targeting and prolonged therapeutic action, making this nanomedicine a promising candidate for clinical translation in the treatment of TBI.