The PLLA/Gel@BBR 3D Nanoscaffold Protects Hair Cells From Neomycin Damage by Reducing Oxidative Stress

Sensorineural hearing loss (SNHL) is the most prevalent form of hearing impairment observed in clinical practice. The primary pathological characteristic of this condition is the irreversible damage to the cochlear hair cells (HCs) and the associated spiral ganglion neurons (SGNs). Since HCs in the mammalian inner ear lack intrinsic regenerative capacity, damage to these cells often results in irreversible hearing loss. In recent years, two-dimensional (2D) culture systems have made substantial progress in supporting the regeneration of auditory cells. However, the regenerated HCs in these 2D systems fail to develop fully mature, functional stereociliary bundles and do not form synaptic connections with SGNs. As a result, they cannot achieve true physiological restoration of hearing. Therefore, the development of three-dimensional (3D) systems that replicate the inner ear microenvironment is essential for investigating therapeutic methods against SNHL. In this study, we aim to prepare 2D electrospun nanofiber membranes using electrospinning technology, and then these 2D nanofiber membranes were successfully converted into 3D PLLA/Gel@BBR nanoscaffolds via freeze-drying. We subsequently assessed the effects of the inner ear organoid on HC growth and neomycin (Neo)-induced ototoxicity. Our findings indicate that the inner ear organoid effectively mimics the physiological microenvironment of the genuine organ of Corti in the inner ear. This inner ear organoid can facilitate drug sustained-release and protect damaged auditory cells from ototoxic damage. This research offers promising insights for developing innovative strategies to protect auditory cells and treat SNHL.