Tissue Engineering Evaluation of Material Implants for Vocal Fold Restoration

项目总结 当声带(VF)固有层(LP)的成分、几何形状和粘弹性发生改变时 对于疤痕，VF的振动功能可能会严重中断，由此导致的发音困难从 声音沙哑到失声。VF瘢痕形成已被证明很难用目前的外科技术和标准来治疗 增强物质(如胶原蛋白、脂肪)。由于患上嗓音的患者人数众多 继发于疤痕的损伤，增强材料的发展为独特的优化 目前正在积极调查有限责任公司的要求。 我们建议对VF成纤维细胞的特定材料特性进行系统和定量的评估 (VFF)行为趋向合理的种植体设计。我们的基本前提是，为了合理地开发一种 设计师材料适合修复有疤痕的腰椎，我们需要了解的不仅仅是材料是否符合 LP独特的力学性能环境也影响着关键材料的设计 影响VFF胞外基质产生和表型的参数。具体地说，VFF对 材料参数的数量，例如孔大小、生化刺激和降解率，可以 成功地在体外进行了测试，并将形成这一建议的基础。然后，可以使用结果来指导 材料的设计和体内试验的预筛选材料。 我们将采用一系列受控的、系统的修改形成的基础材料 二丙烯酸酯衍生聚乙二醇(PEGDA)大分子单体。重要的是，PEGDA水凝胶 固有的对蛋白质吸附的抵抗力，导致了一种生物空白石板，可以在 控制方式以包含特定的生化刺激。此外，孔的大小和降解率 PEGDA水凝胶可以进行系统的改性，使聚乙二醇基材料成为系统材料的理想选择 物业--细胞反应调查。项目叙事 继发于声带(VF)固有层(LP)疤痕形成的慢性嗓音障碍可能会使人虚弱 在生活质量方面，事实证明，用目前的手术范例很难治疗，结果是 设计生物材料植入物等替代疗法正在积极研究中。我们建议 进行受控的体外组织工程(TE)实验和定量评估特定的 材料特性对声带成纤维细胞行为的影响 材料。这项关于材料特性输入对细胞行为的改变的独立调查是 其设计独一无二，对一系列组织再生应用具有重要意义。

PROJECT SUMMARY When the vocal fold (VF) lamina propria (LP) composition, geometry, and viscoelasticity are altered due to scarring, VF vibratory function can be severely disrupted, with resultant dysphonias ranging from hoarseness to voice loss. VF scarring has proven difficult to treat with current surgical techniques and standard augmentation substances (e.g., collagen, fat). Due to the size of the patient population suffering from voice impairment secondary to scarring, the development of augmentation materials optimized for the unique requirements of the LP is currently being actively investigated. We propose the systematic and quantitative assessment of specific material properties on VF fibroblast (VFF) behavior towards rational implant design. Our underlying premise is that in order to rationally develop a designer material suitable for restoration of scarred LP, we need to understand not only if the material meets the unique mechanical property environment of the LP but also the impact of critical material design parameters on VFF extracellular matrix production and phenotype. Specifically, the response of VFFs to a number of material parameters, such as pore size, biochemical stimuli, and degradation rate, can be successfully assayed in vitro and will form the basis of this proposal. The results can then used to guide the design of materials and to pre-screen materials for in vivo trials. We will employ a series of controlled, systematic modifications of a base material formed from diacrylate-derivatized poly(ethylene glycol) (PEGDA) macromers. Importantly, PEGDA hydrogels are intrinsically resistant to protein adsorption, resulting in a biological ¿blank slate¿ which can be modified in a controlled manner to contain defined biochemical stimuli. In addition the pore size and degradation rate of PEGDA hydrogels can be systematically modified, making PEG-based materials ideal for systematic material property-cell response investigations. PROJECT NARRATIVE Chronic voice impairment secondary to vocal fold (VF) lamina propria (LP) scarring can be debilitating in terms of quality of life and has proven difficult to treat with current surgical paradigms, with the result that alternate treatments such as designer biomaterial implants are being actively investigated. We propose to conduct controlled in vitro tissue engineering (TE) experiments for and quantitative assessment of specific material properties on vocal fold fibroblast cell behavior toward the rational systematic design of LP restoration materials. This proposed uncoupled investigation of alterations in material property inputs on cell behavior is unique in its design and has significance for a range of tissue regeneration applications.