ABSTRACT

Brain injuries, and neurodegenerative diseases can result in significant disability, lowered quality of life, and mortality. Current treatments including autologous nerve grafts are insufficient. This work presents the creation of new biomimetic supramolecular assemblies as a scaffold for potential applications in neural tissue regeneration. It is composed of polyethylene glycol amide core-conjugated with a thiazole-based building block and a peptide sequence (RVYNMGKGKGFCVPRPLVVYR). This peptide sequence is derived from laminin, a basal membrane protein, and a component of the extracellular matrix of neuronal cells. The product formed was allowed to self-assemble and bound to polypyrrole by layer-by-layer assembly to impart conductive properties (Lam-PEG-thiazole-PPy) resulting in the formation of fibrillar assemblies as indicated by electron microscopy studies. Rheological studies demonstrated that incorporation of PPy resulted in higher storage modulus indicative of higher ability to store deformation energy. Culture of rat olfactory-bulb derived neurons with the assemblies demonstrated that the Lam-PEG-thiazole-PPy assemblies promoted cell proliferation and were able to interact favorably with the cells. After 10 days of culture with the assemblies interconnected networks could be visualized. Furthermore, electrical stimulation resulted in a significant increase in axonal outgrowths. Thus, the assemblies presented herein exhibit potential for applications as a novel scaffold for neural tissue engineering.

摘要

脑损伤和神经退行性疾病可导致严重残疾、生活质量下降和死亡率。目前的治疗包括自体神经移植是不够的。这项工作提出了创建新的仿生超分子组件作为神经组织再生潜在应用的支架。它由聚乙二醇酰胺核与基于噻唑的结构单元和肽序列 (RVYNMGKGKGFCVPRPLVVYR) 缀合组成。该肽序列来源于层粘连蛋白，一种基底膜蛋白，也是神经元细胞的细胞外基质的一种成分。使形成的产物自组装并通过逐层组装与聚吡咯结合以赋予导电性能（Lam-PEG-噻唑-PPy），导致形成如电子显微镜研究所示的纤维状组装体。流变学研究表明，PPy 的掺入导致更高的储能模量，表明更高的储存变形能的能力。具有装配体的大鼠嗅球衍生神经元的培养表明，Lam-PEG-噻唑-PPy 装配体促进细胞增殖并且能够与细胞有利地相互作用。经过 10 天的培养与程序集互连网络可以可视化。此外，电刺激导致轴突生长显着增加。因此，