Departments of Chemical and Biochemical Engineering, ‡Otolaryngology Head and Neck Surgery, and §Neurosurgery, University of Iowa , Iowa City, Iowa 52242, United States.
ACS Appl Mater Interfaces. 2017 Sep 20;9(37):31488-31496. doi: 10.1021/acsami.7b09258. Epub 2017 Sep 5.
Cochlear Implants (CIs) suffer from limited tonal resolution due, in large part, to spatial separation between stimulating electrode arrays and primary neural receptors. In this work, a combination of physical and chemical micropatterns, formed on acrylate polymers, are used to direct the growth of primary spiral ganglion neurons (SGNs), the inner ear neurons. Utilizing the inherent temporal and spatial control of photopolymerization, physical microgrooves are fabricated using a photomask in a single step process. Biochemical patterns are generated by adsorbing laminin, a cell adhesion protein, to acrylate polymer surfaces followed by irradiation through a photomask with UV light to deactivate protein in exposed areas and generate parallel biochemical patterns. Laminin deactivation was shown increase as a function of UV light exposure while remaining adsorbed to the polymer surface. SGN neurites show alignment to both biochemical and physical patterns when evaluated individually. Competing biochemical and physical patterns were also examined. The relative guiding strength of physical cues was varied by independently changing both the amplitude and the band spacing of the microgrooves, with higher amplitudes and shorter band spacing providing cues that more effective guide neurite growth. SGN neurites aligned to laminin patterns with lower physical pattern amplitude and thus weaker physical cues. Alignment of SGNs shifted toward the physical pattern with higher amplitude and lower periodicity patterns which represent stronger cues. These results demonstrate the ability of photopolymerized microfeatures to modulate alignment of inner ear neurites even in the presence of conflicting physical and biochemical cues laying the groundwork for next generation cochlear implants and neural prosthetic devices.
人工耳蜗（CIs）由于刺激电极阵列和初级神经受体之间的空间分离，在很大程度上受到有限的音调分辨率的限制。在这项工作中，在丙烯酸酯聚合物上形成的物理和化学微图案的组合被用于引导初级螺旋神经节神经元（SGNs），内耳神经元的生长。利用光聚合的固有时间和空间控制，通过光掩模在一步过程中制造物理微槽。通过将层粘连蛋白（一种细胞粘附蛋白）吸附到丙烯酸酯聚合物表面并通过光掩模用紫外光照射来生成平行的生化图案，从而生成生化图案。层粘连蛋白失活被证明随着紫外光暴露而增加，同时仍吸附在聚合物表面上。当单独评估时，SGN 神经突显示出对生化和物理图案的对齐。还检查了竞争的生化和物理模式。通过独立改变微槽的幅度和带宽来改变物理线索的相对引导强度，较高的幅度和较短的带宽提供了更有效地引导神经突生长的线索。SGN 神经突与具有较低物理图案幅度和因此较弱物理线索的层粘连蛋白图案对齐。SGNs 的对齐随着具有较高幅度和较低周期性图案的物理图案而向物理图案移动，这些图案代表更强的线索。这些结果表明，光聚合微特征即使在存在相互竞争的物理和生化线索的情况下，也能够调节内耳神经突的对齐，为下一代耳蜗植入物和神经假体设备奠定了基础。
