Engineering exosomes in the treatment of sensorineural hearing loss: from basic research to clinical applications

Engineered exosomes demonstrate good biocompatibility, barrier-crossing ability, and programmable drug-loading capacity. Recently, they have steadily emerged as a promising area of study for precision intervention in sensorineural hearing loss. This review focuses on numerous main topics, including the selection of exosome sources and donor-cell pretreatment techniques, surface targeting strategies, therapeutic cargo loading methods, the mechanisms by which exosomes cross the blood-labyrinth barrier, and recent advancements in research on the role of exosomes in hair cell protection, spiral ganglion neuron protection, supporting-cell plasticity, and cochlear microenvironment remodeling. This review also examines the key challenges in the clinical translation of exosomes. It comprehensively reviews direct cochlear exosome evidence for hair cell protection and auditory protection, separating these results from indirect non-cochlear exosome evidence and theoretical engineering approaches for spiral ganglion neuron protection, supporting-cell-mediated regeneration-related mechanisms, and cochlear neurovascular microenvironment remodeling. In addition to outlining a framework that combines targeted delivery and functional regulation for sensorineural hearing loss, this review highlights the hearing-protective potential of engineered exosomes in preclinical models and requires further experimental validation. Despite the positive outlook, there are still notable issues with the durability of therapeutic effects, mechanistic clarity, and clinical translatability. Future studies should prioritize standardization of extracellular vesicle reporting, dose reproducibility, clinically relevant models, and long-term functional outcomes.