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生物功能化的基于肽的水凝胶提供了允许性支架,以吸引螺旋神经节神经元的神经突生长。

Biofunctionalized peptide-based hydrogels provide permissive scaffolds to attract neurite outgrowth from spiral ganglion neurons.

作者信息

Frick Claudia, Müller Marcus, Wank Ute, Tropitzsch Anke, Kramer Benedikt, Senn Pascal, Rask-Andersen Helge, Wiesmüller Karl-Heinz, Löwenheim Hubert

机构信息

Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany.

EMC microcollections GmbH, DE-72070 Tübingen, Germany.

出版信息

Colloids Surf B Biointerfaces. 2017 Jan 1;149:105-114. doi: 10.1016/j.colsurfb.2016.10.003. Epub 2016 Oct 4.

Abstract

Cochlear implants (CI) allow for hearing rehabilitation in patients with sensorineural hearing loss or deafness. Restricted CI performance results from the spatial gap between spiral ganglion neurons and the CI, causing current spread that limits spatially restricted stimulation and impairs frequency resolution. This may be substantially improved by guiding peripheral processes of spiral ganglion neurons towards and onto the CI electrode contacts. An injectable, peptide-based hydrogel was developed which may provide a permissive scaffold to facilitate neurite growth towards the CI. To test hydrogel capacity to attract spiral ganglion neurites, neurite outgrowth was quantified in an in vitro model using a custom-designed hydrogel scaffold and PuraMatrix. Neurite attachment to native hydrogels is poor, but significantly improved by incorporation of brain-derived neurotrophic factor (BDNF), covalent coupling of the bioactive laminin epitope IKVAV and the incorporation a full length laminin to hydrogel scaffolds. Incorporation of full length laminin protein into a novel custom-designed biofunctionalized hydrogel (IKVAV-GGG-SIINFEKL) allows for neurite outgrowth into the hydrogel scaffold. The study demonstrates that peptide-based hydrogels can be specifically biofunctionalized to provide a permissive scaffold to attract neurite outgrowth from spiral ganglion neurons. Such biomaterials appear suitable to bridge the spatial gap between neurons and the CI.

摘要

人工耳蜗(CI)可使感音神经性听力损失或失聪患者实现听力康复。人工耳蜗性能受限是由于螺旋神经节神经元与人工耳蜗之间存在空间间隙,导致电流扩散,从而限制了空间受限刺激并损害频率分辨率。通过引导螺旋神经节神经元的外周突起朝向并附着于人工耳蜗电极触点,这种情况可能会得到显著改善。已开发出一种基于肽的可注射水凝胶,它可为神经突向人工耳蜗生长提供适宜的支架。为测试水凝胶吸引螺旋神经节神经突的能力,在体外模型中使用定制设计的水凝胶支架和PuraMatrix对神经突生长进行了定量分析。神经突对天然水凝胶的附着性较差,但通过掺入脑源性神经营养因子(BDNF)、生物活性层粘连蛋白表位IKVAV的共价偶联以及将全长层粘连蛋白掺入水凝胶支架,附着性得到显著改善。将全长层粘连蛋白掺入新型定制设计的生物功能化水凝胶(IKVAV-GGG-SIINFEKL)中可使神经突生长入水凝胶支架。该研究表明,基于肽的水凝胶可进行特异性生物功能化,以提供适宜的支架来吸引螺旋神经节神经元的神经突生长。此类生物材料似乎适合弥合神经元与人工耳蜗之间的空间间隙。

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