Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, 30625 Hannover, Germany.
Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625 Hannover, Germany.
Biomolecules. 2022 Apr 17;12(4):589. doi: 10.3390/biom12040589.
Cochlear hair cell damage and spiral ganglion neuron (SGN) degeneration are the main causes of sensory neural hearing loss. Cochlear implants (CIs) can replace the function of the hair cells and stimulate the SGNs electrically. The condition of the SGNs and their spatial distance to the CI are key factors for CI-functionality. For a better performance, a high number of neurons and a closer contact to the electrode are intended. Neurotrophic factors are able to enhance SGN survival and neurite outgrowth, and thereby might optimize the electrode-nerve interaction. This would require chronic factor treatment, which is not yet established for the inner ear. Investigations on chronic drug delivery to SGNs could benefit from an appropriate in vitro model. Thus, an inner ear inspired Neurite Outgrowth Chamber (NOC), which allows the incorporation of a mini-osmotic pump for long-term drug delivery, was designed and three-dimensionally printed. The NOC's function was validated using spiral ganglion explants treated with ciliary neurotrophic factor, neurotrophin-3, or control fluid released via pumps over two weeks. The NOC proved to be suitable for explant cultivation and observation of pump-based drug delivery over the examined period, with neurotrophin-3 significantly increasing neurite outgrowth compared to the other groups.
耳蜗毛细胞损伤和螺旋神经节神经元（SGN）变性是感觉神经性听力损失的主要原因。耳蜗植入物（CI）可以替代毛细胞的功能，并通过电刺激 SGN。SGN 的状况及其与 CI 的空间距离是 CI 功能的关键因素。为了获得更好的性能，期望有更多的神经元和更接近电极的接触。神经营养因子能够增强 SGN 的存活和轴突生长，从而优化电极-神经的相互作用。这需要进行慢性因子治疗，但尚未在内耳中建立。对 SGN 的慢性药物输送的研究可能受益于适当的体外模型。因此，设计并三维打印了一种内耳启发的轴突生长室（NOC），该室允许装入微型渗透泵以进行长期药物输送。使用毛细胞神经生长因子、神经营养因子-3 或通过泵释放的对照液处理螺旋神经节外植体两周，验证了 NOC 的功能。NOC 被证明适合于外植体培养和观察在检查期间基于泵的药物输送，与其他组相比，神经营养因子-3 显著增加了轴突生长。
