The role of natural and engineered exosomes in repairing damage to the nervous system

Following neurological injury, neuronal cell death and neuroinflammation mutually reinforce each other, further exacerbating neurological damage. Concurrently, the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) impede drug penetration into the injured region, rendering neurological injury challenging to treat. Natural exosomes can penetrate biological barriers and deliver bioactive molecules to target sites, offering new possibilities for treatment. Engineered modifications further enhance the bioactivity and targeting capabilities of exosomes. Both natural and engineered exosomes, as a cell-free therapy, hold great promise for applications in the repair of neurological injuries. This review summarizes exosomes from different cellular sources and their engineering strategies, discusses the neuroinflammatory regulation and neuroprotective effects of natural and engineered exosomes, reviews the current status of exosome clinical research and key areas for clinical translation, with the aim of providing new insights for the clinical treatment and research of neural injury.