Drug Loaded, Biodegradable Nerve Conduits for the Simultaneous Chemical and Electrical Stimulation of Neural Cells as a Therapeutic Approach for Peripheral Nerve Regeneration

Drug Loaded, Biodegradable Nerve Conduits for the Simultaneous Chemical and Electrical Stimulation of Neural Cells as a Therapeutic Approach for Peripheral Nerve Regeneration
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载药、可生物降解的神经导管,用于同时化学和电刺激神经细胞,作为周围神经再生的治疗方法

DOI:
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发表时间:
2010
期刊:
影响因子:
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通讯作者:
R. Zehbe
R. Zehbe
中科院分区:
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文献类型:
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作者:
Franziska Schmidt;Zahra Ghalanbor;F. Thormann;Markus Kühbacher;R. Bodmeier;U. Gross;H. Schubert;R. Zehbe

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周围神经损伤的修复是再生医学的重要研究领域。一种治疗方法是使用由生物可降解聚合物组成的组织工程神经导管。这些材料可被设计成包括活性剂以进一步刺激或影响这些神经导管中特定神经元细胞的增殖、成熟、分化或迁移。我们开发了一种在自结构微电极上电存款和修饰神经细胞和细胞外基质蛋白的方法。这些电极也提供了一种可行的方法来研究神经细胞的电刺激。在我们的方法中,聚-D,L-丙交酯-共-乙交酯(PLGA)作为这些电极的可能基板进行了研究,同时进一步允许在药物释放概念中整合模型物质。在第一种方法中,使用咖啡因,因为其对某些神经元细胞的刺激和抑制作用是众所周知的,同时还允许通过化学手段容易地掺入PLGA中。采用Plackett-Burman实验设计,在药物浓度、聚合物浓度、溶剂类型和薄膜干燥条件等不同参数之间寻找最佳组合物。测试了优化的载药聚合物膜的释放和降解曲线,以及它们在细胞培养中的行为。最后,我们目前正在建立一个综合的实验装置,结合咖啡因修饰的PLGA膜基板的电极结构的制造,以调查细胞沉积通过电气手段和刺激/抑制通过化学释放。
Restoring peripheral nerve trauma is an important research field in regenerative medicine. One therapeutical approach is to use tissue engineered nerve conduits consisting of biodegradable polymers. These materials can be designed to include active agents to further stimulate or influence proliferation, maturation, differentiation or migration of specific neuronal cell in these nerve guides. We have developed a method to electrically deposit and immobilize neuronal cells and extracellular matrix proteins on self structured micro electrodes. These electrodes also present a feasible methodology to investigate electrical stimulation of nerve cells. In our approach, poly-D,L-lactide-co-glycolides (PLGA) were investigated as possible substrate for these electrodes, while further allowing for the integration of model substances in a drug release concept. In a first approach, caffeine was used due to its well known effect of both stimulating and inhibiting effects on certain neuronal cells, while also allowing easy incorporation into PLGA via chemical means. A Plackett-Burman experimental design was used to find the optimum composition among different parameters such as drug concentration, polymer concentration, type of solvent and film-drying condition. The optimized drug loaded polymer films were tested for their release and degradation profile, and their behavior in cell culture. Finally, we are currently establishing an integrated experimental setup, combining caffeine modified PLGA film substrates with the manufacturing of the electrode structures to investigate cell deposition via electrical means and stimulation/ inhibition via chemical release.
DOI: 10.1002/jbm.a.31298
发表时间: 2008-03-01
影响因子: 4.9
作者:
de Ruiter, Godard C.;Onyeneho, Irene A.;Windebank, Anthony J.
通讯作者: Windebank, Anthony J.