Wille Inga, Harre Jennifer, Oehmichen Sarah, Lindemann Maren, Menzel Henning, Ehlert Nina, Lenarz Thomas, Warnecke Athanasia, Behrens Peter
Institut für Anorganische Chemie, Leibniz Universität Hannover, Hannover, Germany.
Cluster of Excellence Hearing4all, Hannover, Germany.
Front Bioeng Biotechnol. 2022 Jan 24;10:776890. doi: 10.3389/fbioe.2022.776890. eCollection 2022.
State-of-the-art treatment for sensorineural hearing loss is based on electrical stimulation of residual spiral ganglion neurons (SGNs) with cochlear implants (CIs). Due to the anatomical gap between the electrode contacts of the CI and the residual afferent fibers of the SGNs, spatial spreading of the stimulation signal hampers focused neuronal stimulation. Also, the efficiency of a CI is limited because SGNs degenerate over time due to loss of trophic support. A promising option to close the anatomical gap is to install fibers as artificial nerve guidance structures on the surface of the implant and install on these fibers drug delivery systems releasing neuroprotective agents. Here, we describe the first steps in this direction. In the present study, suture yarns made of biodegradable polymers (polyglycolide/poly-ε-caprolactone) serve as the basic fiber material. In addition to the unmodified fiber, also fibers modified with amine groups were employed. Cell culture investigations with NIH 3T3 fibroblasts attested good cytocompatibility to both types of fibers. The fibers were then coated with the extracellular matrix component heparan sulfate (HS) as a biomimetic of the extracellular matrix. HS is known to bind, stabilize, modulate, and sustainably release growth factors. Here, we loaded the HS-carrying fibers with the brain-derived neurotrophic factor (BDNF) which is known to act neuroprotectively. Release of this neurotrophic factor from the fibers was followed over a period of 110 days. Cell culture investigations with spiral ganglion cells, using the supernatants from the release studies, showed that the BDNF delivered from the fibers drastically increased the survival rate of SGNs . Thus, biodegradable polymer fibers with attached HS and loaded with BDNF are suitable for the protection and support of SGNs. Moreover, they present a promising base material for the further development towards a future neuronal guiding scaffold.
感音神经性听力损失的先进治疗方法是基于使用人工耳蜗(CI)对残余螺旋神经节神经元(SGN)进行电刺激。由于CI的电极触点与SGN的残余传入纤维之间存在解剖学间隙,刺激信号的空间扩散阻碍了聚焦的神经元刺激。此外,CI的效率受到限制,因为由于营养支持的丧失,SGN会随着时间的推移而退化。一个有前景的缩小解剖学间隙的选择是在植入物表面安装纤维作为人工神经引导结构,并在这些纤维上安装释放神经保护剂的药物递送系统。在此,我们描述了朝着这个方向迈出的第一步。在本研究中,由可生物降解聚合物(聚乙交酯/聚-ε-己内酯)制成的缝合线用作基本纤维材料。除了未改性的纤维外,还使用了用胺基改性的纤维。用NIH 3T3成纤维细胞进行的细胞培养研究证明这两种类型的纤维都具有良好的细胞相容性。然后将纤维用细胞外基质成分硫酸乙酰肝素(HS)包被,作为细胞外基质的仿生材料。已知HS能结合、稳定、调节并持续释放生长因子。在此,我们将携带HS的纤维负载脑源性神经营养因子(BDNF),已知该因子具有神经保护作用。在110天的时间内跟踪了这种神经营养因子从纤维中的释放情况。使用释放研究的上清液对螺旋神经节细胞进行的细胞培养研究表明,从纤维中递送的BDNF显著提高了SGN的存活率。因此,附着有HS并负载有BDNF的可生物降解聚合物纤维适用于SGN的保护和支持。此外,它们为未来神经元引导支架的进一步开发提供了一种有前景的基础材料。