Tissue Engineering Evaluation of Material Implants for Vocal Fold Restoration

声带修复材料植入物的组织工程评估

• 批准号: 7850307
• 负责人: Mariah S Hahn
• 金额: $ 3.66万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7850307
• 关键词: Adhesions; Adsorption; Affect; Behavior; Biochemical; Biocompatible Materials; Biological; Biomechanics; Caliber; Cells; Characteristics; Chronic; Cicatrix; Classification; Collagen; Collagen Fibril; Complex; Data; Development; Disease; Dysphonia; Encapsulated; Environment; Ethylene Glycols; Evaluation; Exposure to; Extracellular Matrix; Family suidae; Fatty acid glycerol esters; Fibroblasts; Fibronectins; Goals; Grant; Healed; Hoarseness; Human; Hyaluronan; Hydrogels; Impairment; Implant; In Vitro; Individual; Invaded; Investigation; Lamina Propria; Light; Liquid substance; Mechanics; Modification; Natural regeneration; Operative Surgical Procedures; Phenotype; Physiology; Pliability; Polyethylene Glycols; Population; Porosity; Production; Property; Proteins; Quality of life; Regulation; Research Personnel; Resistance; Role; Route; Screening procedure; Secondary to; Series; Stimulus; Structure; Techniques; Testing; Time; Tissue Engineering; Tissues; Voice; Voice Quality; alternative treatment; base; cell behavior; combinatorial; crosslink; decorin; design; ethylene glycol; healing; implant material; in vitro Assay; in vivo; meetings; patient population; research study; response; restoration; scaffold; tissue regeneration; vibration; viscoelasticity; vocal cord

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.

项目摘要 当声带（VF）固有层（LP）组成，几何和粘弹性时 要疤​​痕，VF振动功能可能会严重中断，导致的吞咽困难范围从 嘶哑的声音损失。事实证明，VF疤痕很难用当前的手术技术和标准治疗 增强物质（例如胶原蛋白，脂肪）。由于患者人口的大小 继发于疤痕的损害，为独特而优化的增强材料的开发 目前正在积极调查LP的要求。 我们提出了VF成纤维细胞上特定材料特性的系统和定量评估 （VFF）对理性植入物设计的行为。我们的基本前提是，为了合理地发展一个 设计师的材料适合恢复疤痕LP，我们不仅需要了解材料相遇的情况 LP的独特机械性能环境，也是关键材料设计的影响 VFF细胞外基质产生和表型的参数。具体而言，VFF对A的响应 物质参数的数量，例如孔径，生化刺激和降解率，可以是 在体外成功分配，将构成该提案的基础。然后可以使用结果来指导 材料的设计和用于体内试验的屏幕前材料。 我们将采用一系列受控的，系统的修改，对由 二丙酸酯衍生化的聚乙二醇（PEGDA）宏观分子。重要的是，PEGDA水凝胶是 对蛋白质吸附的本质抗性，导致生物学»空白板可以在A中进行修改 控制方式以包含定义的生化刺激。另外，孔径和降解速率 PEGDA水凝胶可以系统地修饰，使基于PEG的材料非常适合系统材料 物业细胞响应调查。项目叙述 慢性声音障碍继发于声带（VF）lamina propria（LP）疤痕可能会使人衰弱 就生活质量而言，事实证明很难通过当前的手术范例来治疗，结果 正在积极研究诸如设计师生物材料工具之类的替代治疗方法。我们建议 进行受控的体外组织工程（TE）实验，以对特定的特定评估进行定量评估 声带褶皱成纤维细胞的材料特性，用于LP修复的合理系统设计 材料。这项提出的对细胞行为材料特性输入的变化的未耦合研究是 其设计独特，对于一系列组织再生应用具有重要意义。