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负载神经干细胞的导电水凝胶人工耳蜗电极涂层的制备与表征

Preparation and characterization of neural stem cell-loaded conductive hydrogel cochlear implant electrode coatings.

作者信息

Wang Zhiyi, Yan Yu, Chen Wenxin, Tan Zhiping, Yan Qingfeng, Chen Qingqing, Ding Xue, Shen Jiahua, Gao Min, Yang Yang, Yu Lulu, Lin Fuzhi, Fu Yong, Jin Xiaoqiang, Yu Xiaohua

机构信息

The Children's Hospital of Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China.

Zhejiang Nurotron Biotechnology Co., Ltd, Hangzhou 311121, Zhejiang Province, China.

出版信息

Biomater Adv. 2025 Feb;167:214109. doi: 10.1016/j.bioadv.2024.214109. Epub 2024 Nov 8.

Abstract

Sensorineural deafness is a hearing impairment resulting from damage to the auditory nerve or inner ear hair cells. Currently, cochlear implants (CIs) are widely used as hearing aids for sensorineural deafness patients. A fundamental limitation of cochlear implants (CIs) is that spiral ganglion neurons (SGNs) cannot be replenished. This greatly restricts the rehabilitation of sensorineural deafness. Additionally, the insertion of CIs can cause secondary cochlear damage, worsening the condition of the patients' cochlear. Therefore, a new type of neural stem cells (NSCs) loaded graphene oxide-polyaniline/GelMA (GO-PAni/GelMA) conductive hydrogel electrode for cochlear implant was fabricated via in-situ radical polymerization and cyclic UV curing technique. On the one hand, the hydrogel electrode, as a direct contact layer, helps to avoid the physical hurt for cochlear. On the other hand, NSCs were supplemented via the hydrogel carrier and neuronal differentiation was induced by electrical stimulation, which was validated by the experimental results of immunofluorescence, Phalloidin Staining and RT-qPCR. Furthermore, based on RNA sequencing and transcriptome analysis, we hypothesized that the neuronal differentiation of NSCs was adjusted by the calcium signaling pathway and GABAergic synapse. Overall, our cell loading conductive hydrogel electrode may be an effective solution to sensorineural deafness. The revelation of the mechanism of neuronal differentiation promoted by electrical stimulation provides a basis for further sensorineural deafness treatment using conductive hydrogel CI electrode.

摘要

感音神经性耳聋是一种由听神经或内耳毛细胞受损导致的听力障碍。目前,人工耳蜗(CI)作为感音神经性耳聋患者的助听器被广泛使用。人工耳蜗(CI)的一个基本局限性在于螺旋神经节神经元(SGN)无法补充。这极大地限制了感音神经性耳聋的康复。此外,人工耳蜗的植入会导致继发性耳蜗损伤,使患者的耳蜗状况恶化。因此,通过原位自由基聚合和循环紫外光固化技术制备了一种新型的负载神经干细胞(NSC)的氧化石墨烯-聚苯胺/明胶甲基丙烯酰基(GO-PAni/GelMA)导电水凝胶电极用于人工耳蜗。一方面,水凝胶电极作为直接接触层,有助于避免对耳蜗的物理伤害。另一方面,通过水凝胶载体补充神经干细胞,并通过电刺激诱导神经元分化,免疫荧光、鬼笔环肽染色和RT-qPCR的实验结果验证了这一点。此外,基于RNA测序和转录组分析,我们假设神经干细胞的神经元分化是由钙信号通路和γ-氨基丁酸能突触调节的。总体而言,我们的细胞负载导电水凝胶电极可能是解决感音神经性耳聋的有效方案。电刺激促进神经元分化机制的揭示为进一步使用导电水凝胶人工耳蜗电极治疗感音神经性耳聋提供了依据。

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