Highly resilient, hydrophilic bioelastomers for engineering vocal fold tissue

用于工程声带组织的高弹性、亲水性生物弹性体

基本信息

批准号：
8295660
负责人：
Kristi L Kiick
金额：
$ 48.99万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-20 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8295660
关键词：
Address Behavior Binding Biological Biological Assay Biomedical Engineering Bioreactors Cell Culture Techniques Cells Cicatrix Connective Tissue Cultured Cells Deposition Development Disease Encapsulated Engineering Environment Environmental Risk Factor Evaluation Extracellular Matrix Fatigue Fibroblasts Frequencies Gel Gene Expression Gene Proteins Health Heparin Binding Human Hydrogels In Situ Individual Injectable Injection of therapeutic agent Insect Proteins Insecta Investigation Laboratories Lamina Propria Living Standards Mechanical Stimulation Mechanical Stress Mechanics Mesenchymal Stem Cells Methodology Methods Modeling Natural regeneration Occupational Operative Surgical Procedures Organ Oryctolagus cuniculus Outcome Phenotype Pliability Production Productivity Property Proteins Recombinants Recovery Regenerative Medicine Research Resistance Rheology Sampling Stretching Techniques Testing Tissue Engineering Tissues United States Voice Voice Disorders Western Blotting Work base cell type comparative cost design elastomeric in vivo interest method development novel polypeptide programs protein expression resilience resilin scaffold social sound success teacher tissue regeneration vocal cord

项目摘要

DESCRIPTION (provided by applicant): Impaired voice production holds significant implications for individual health and wellness, social and occupational function, and societal productivity; the societal costs of voice problems in teachers alone have been estimated to be of the order of $2.5 billion annually in the United States. The development of materials for the treatment of vocal fold disorders, however, has been hampered by the stringent mechanical requirements of the vocal fold, which include the ability to both sustain deformation at frequencies as high as 1000Hz, and also completely recoil after transient stretch up to 200%. To date, despite widespread efforts in the development of materials scaffolds for the tissue engineering of the vocal fold, no materials with the required mechanical properties have been identified. We propose a comprehensive bioengineering approach to this problem. We will employ new elastomeric scaffolds based on the insect protein, resilin, which is the primary energy store in the sound-producing, jumping, and flight organs of insects, and demonstrates unmatched resilience (recovery after stretch) after deformation at frequencies up to 4000Hz. We will employ modular recombinant methods to generate resilin- like polypeptides (RLPs) that can be engineered to carry biologically active domains without compromising the mechanical properties of the resilin domain, and in which independent tuning of multiple properties of these matrices, including mechanical properties, cell binding, and degradation, is possible. We will culture human mesenchymal stem cells (hMSCs) in these matrices under both static and dynamic conditions, and employ a suite of oscillatory rheology, tensile testing, and high-frequency torsional-wave methods to characterize the mechanical properties of cell-encapsulated constructs. Histological, immunohistological, western blot, and gene expression techniques will be employed to confirm the differentiation of hMSCs and the production of vocal fold extracellular matrix. These studies will inform our choices of cell/materials constructs for injection into the vocal folds of rabbits to ameliorate vocal fold scarring. Our investigations wil thus contribute to the development of methods to characterize and culture materials at high frequencies, as well as yield a new class of materials that may optimize the regeneration of vocal fold tissue. Our approaches ultimately will be useful as a general platform in the design of materials for mechanically demanding regenerative medicine applications.

描述（由申请人提供）：语音生产受损对个人健康和健康，社会和职业功能以及社会生产力具有重大影响；据估计，仅在美国，仅教师的语音问题的社会成本在美国每年为25亿美元。然而，人声折的严格的机械要求阻碍了人声折叠障碍的材料的开发，其中包括能够在高达1000Hz的频率下保持变形的能力，以及在短暂的延伸后完全退缩到200％。迄今为止，尽管在开发声带的组织工程材料脚手架上的开发方面很广泛，但尚未确定具有所需机械性能的材料。我们建议解决此问题的全面生物工程方法。我们将基于昆虫蛋白Resilin的新弹性支架，这是昆虫的发声，跳跃和飞行器官中的主要能量存储，并在最高4000Hz的频率下表现出无与伦比的弹性（拉伸后恢复）。我们将采用模块化重组方法来生成像溶质蛋白的多肽（RLP），可以设计用于携带生物学活性域而不会损害溶酶硅蛋白结构域的机械性能，并且在其中独立调整这些矩阵的多个属性，包括机械性能，细胞结合和降解，可能是可能的。我们将在静态和动态条件下培养这些矩阵中的人间质干细胞（HMSC），并采用一套振荡性流变学，拉伸测试以及高频扭转波的方法来表征细胞囊化构建体的机械性能。将采用组织学，免疫组织学，蛋白质印迹和基因表达技术来确认HMSC的分化和人声折叠细胞外基质的产生。这些研究将为我们选择细胞/材料构建体的选择，以注入兔子的声带，以改善声带折叠疤痕。因此，我们的研究将有助于开发高频表征和培养材料的方法，并产生一类新的材料，以优化声带组织的再生。最终，我们的方法将作为设计材料设计的一般平台，用于机械苛刻的再生医学应用。