PLLA/Gel@BBR三维纳米支架通过降低氧化应激保护毛细胞免受新霉素损伤

文献信息

中文摘要

背景： 感音神经性听力损失（SNHL）是临床实践中最常见的听力障碍形式。该病症的主要病理特征是耳蜗毛细胞（HCs）及相关螺旋神经节神经元（SGNs）的不可逆损伤。由于哺乳动物内耳中的HCs缺乏内在再生能力，这些细胞的损伤通常导致不可逆的听力损失。近年来，二维（2D）培养系统在支持听觉细胞再生方面取得了实质性进展。然而，这些2D系统中再生的HCs未能发育出完全成熟、功能性的静纤毛束，也未与SGNs形成突触连接。因此，它们无法实现真正的听力生理性恢复。因此，开发模拟内耳微环境的三维（3D）系统对于研究针对SNHL的治疗方法至关重要。在本研究中，我们旨在利用静电纺丝技术制备2D电纺纳米纤维膜，然后通过冷冻干燥将这些2D纳米纤维膜成功转化为3D PLLA/Gel@BBR纳米支架。我们随后评估了内耳类器官对HC生长和新霉素（Neo）诱导的耳毒性的影响。我们的发现表明，内耳类器官有效模拟了内耳中真实Corti器的生理微环境。该内耳类器官可促进药物缓释并保护受损听觉细胞免受耳毒性损伤。这项研究为开发保护听觉细胞和治疗SNHL的创新策略提供了有前景的见解。

英文摘要

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.