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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：
8628100
负责人：
Kristi L Kiick
金额：
$ 47.24万
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/8628100
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）：发声受损对个人健康和保健、社会和职业功能以及社会生产力具有重大影响；据估计，在美国，仅教师的声音问题每年造成的社会成本就达 25 亿美元。然而，用于治疗声带疾病的材料的开发受到声带严格的机械要求的阻碍，其中包括在高达 1000Hz 的频率下维持变形的能力，以及在瞬时拉伸高达 200% 后完全反冲的能力。迄今为止，尽管在声带组织工程材料支架的开发方面做出了广泛的努力，但尚未发现具有所需机械性能的材料。我们提出了解决这个问题的综合生物工程方法。我们将采用基于昆虫蛋白 Resilin 的新型弹性支架，它是昆虫发声、跳跃和飞行器官中的主要能量储存，并在高达 4000Hz 的频率变形后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节肢动物样多肽（RLP），这些多肽可以被设计为携带生物活性结构域，而不损害节肢动物结构域的机械特性，并且可以独立调节这些基质的多种特性，包括机械特性、细胞结合和降解。我们将在静态和动态条件下在这些基质中培养人间充质干细胞（hMSC），并采用一套振荡流变学、拉伸测试和高频扭转波方法来表征细胞封装结构的机械性能。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的分化和声带细胞外基质的产生。这些研究将为我们选择注射到兔子声带以改善声带疤痕的细胞/材料结构提供信息。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，并产生一类可以优化声带组织再生的新型材料。我们的方法最终将成为机械要求较高的再生医学应用材料设计的通用平台。