Tissue Engineering Evaluation of Material Implants for Vocal Fold Restoration

项目摘要 当声带（VF）固有层（LP）的组成、几何形状和粘弹性因 到瘢痕形成，VF振动功能可能严重中断，导致发音困难， 声音嘶哑到失声。VF瘢痕已被证明难以用当前的手术技术和标准治疗 增强物质（例如，胶原、脂肪）。由于患有声音的患者人群的规模 损伤继发于疤痕，增强材料的开发优化了独特的 LP的要求目前正在积极调查中。 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评估 (VFF)合理植入物设计的行为。我们的基本前提是，为了合理地发展一个 设计师材料适合修复疤痕LP，我们不仅需要了解材料是否符合 LP独特的机械性能环境，也是关键材料设计的影响 参数对VFF细胞外基质产生和表型的影响。具体来说，VFF对 许多材料参数，例如孔径、生化刺激和降解速率，可以被 成功地在体外进行了测定，并将构成本提案的基础。然后，结果可以用于指导 材料设计和预筛选材料进行体内试验。 我们将采用一系列的控制，系统的修改形成的基础材料， 二丙烯酸酯衍生的聚乙二醇（PEGDA）大分子单体。重要的是，PEGDA水凝胶是 本质上抵抗蛋白质吸附，导致生物学上的"空白状态"， 控制方式，以包含定义的生化刺激。此外，孔径和降解速率的 PEGDA水凝胶可以系统地改性，使PEG基材料成为系统材料的理想选择。 属性单元响应调查。项目叙述 继发于声带（VF）固有层（LP）瘢痕形成的慢性语音障碍可能会使人衰弱 在生活质量方面，并且已经证明难以用当前的手术范例治疗，结果是， 正在积极研究诸如设计生物材料植入物的替代治疗。我们建议 进行受控的体外组织工程（TE）实验， 材料特性对声带成纤维细胞行为的影响 材料.这一提议的对细胞行为的材料性质输入的改变的非耦合调查是 其设计独特，并且对于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.