ELASTOMERIC POLYMERS & TUNABLE BIOLOGICAL FUNCTIONS FOR VOCAL FOLD TISSUE ENG

弹性聚合物

• 批准号: 8360585
• 负责人: Xinqiao Jia
• 金额: $ 31.05万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360585
• 关键词: Adhesives; Air; Amino Acids; Architecture; Biochemical; Biocompatible Materials; Biological; Biological Factors; Biological Process; Caring; Cell Proliferation; Cells; Centers of Research Excellence; Characteristics; Chemicals; Clinical; Cues; Devices; Disease; Elasticity; Elastin; Elastomers; Engineering; Exhibits; Extracellular Matrix; Faculty; Frequencies; Funding; Grant; Heparin Binding; Hybrids; Lamina Propria; Matrix Metalloproteinases; Mechanical Stimulation; Mechanical Stress; Mechanics; Methods; Molecular; National Center for Research Resources; Natural regeneration; Nature; Organic Chemistry; Pediatric Hospitals; Peptide Synthesis; Peptides; Polymer Chemistry; Polymers; Principal Investigator; Production; Property; Proteins; Research; Research Infrastructure; Resources; Route; Rubber; Source; Stream; Structure; System; Tertiary Protein Structure; Tissue Engineering; Tissues; United States National Institutes of Health; angiogenesis; base; career; cost; crosslink; design; elastomeric; mimetics; novel; polypeptide; resilience; resilin; scaffold; solid state; sound; vocal cord

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. One of the most remarkable mechanical devices that Nature has engineered consists of two small folds of tissue called vocal folds, which are responsible for the production of a great variety of sounds when vibrated by the tracheal air-stream. Under normal conditions, vocal folds can sustain up to 30% strain at frequencies of 100 to 1000 Hz. However, excessive mechanical stresses and deleterious pathological conditions can cause damage to this delicate system, resulting in a wide spectrum of vocal fold disorders. To date, optimal treatment for vocal fold disorders has not yet been realized, and tissue engineering methods hold promise for the regeneration of functional vocal folds. However, the unique biochemical composition, structural organization, and viscoelastic properties of vocal folds have significantly complicated tissue engineering efforts that utilize traditional polymeric biomaterials. In this new collaborative effort that integrates the unique expertise of junior and early-career faculty, we will produce novel bioactive elastomers that can be used as conducive scaffolds for vocal fold tissue engineering. These biomaterials will capture the molecular architecture and mechanical characteristics of natural elastic proteins (elastin and resilin); given the different physicochemical properties of these two proteins, employing both will offer a comprehensive approach for tuning morphological, mechanical and biological properties in the new materials. The elastin mimetic hybrid polymers (EMHP) will comprise a multiblock structure with alternating hydrophobic, elastic synthetic domains and hydrophilic, peptide-based cross-linking domains. The synthetic blocks are expected to show rubber-like elasticity that will functionally mimic the properties of the elastic domains of elastin, while the peptide domains will serve both structural and biological function. In addition, resilin-based modular polypeptides (RBMP) will be produced with multiple repeats of unique functional modules including resilin-based peptide domains, heparin-binding peptides, cell-adhesive peptides, and MMP-sensitive domains in order to produce materials that present useful biological cues while exhibiting high resilience at high frequencies. Our synthetic strategies will exploit the established versatility of synthetic polymer chemistry and solid state peptide synthesis, as well as new orthogonal organic chemistry developed in this COBRE proposal. Chemical methods employing both natural and non-natural amino acids will be used to crosslink EMHP and RBMP to systematically match mechanical properties to those of the natural vocal fold lamina propria. With the aid of clinical collaborators at Christiana Care and the A.I. duPont Hospital for Children, the bioactive elastomers will be evaluated for their ability to promote vocal fold cell proliferation, angiogenesis, and ECM production. These new materials and approaches offer promising routes to ultimately engineering functional vocal fold lamina propria via a combination of viable cells, elastic scaffolds, biological factors and mechanical stimulation.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 大自然设计的最杰出的机械设备之一是由两个小褶皱组成 纸巾称为声褶，当时负责产生各种声音 被气管气流振动。在正常条件下，声带褶皱最多可维持30％的压力 100至1000 Hz的频率。但是，机械应力过多和有害的病理 条件可能会损害这种细腻的系统，从而导致多种声带障碍。到 日期，尚未实现对声带障碍的最佳治疗方法，以及组织工程方法 对功能性声折的再生保持诺言。但是，独特的生化组成， 人声褶皱的结构组织和粘弹性具有明显复杂的组织 利用传统聚合物生物材料的工程工作。 在整合初级和早期教师的独特专业知识的新合作努力中，我们 将产生新型的生物活性弹性体，可以用作声带组织的有益支架 工程。这些生物材料将捕获分子结构和机械特征 天然弹性蛋白（弹性蛋白和溶酶蛋白）；考虑到这两个的不同理化特性 蛋白质采用两者都将提供一种全面的方法来调整形态学，机械和 新材料中的生物特性。弹性蛋白模拟杂交聚合物（EMHP）将包括 多块结构，具有交替的疏水，弹性合成结构域和基于肽的亲水性结构 交联域。预计合成块将显示出橡胶样弹性，从而在功能上将 模仿弹性蛋白的弹性结构域的特性，而肽结构域将两种结构都提供 和生物功能。此外，将使用基于固定蛋白的模块化多肽（RBMP） 多次重复唯一功能模块，包括基于Resilin的肽结构域，肝素结合 肽，细胞粘附肽和MMP敏感结构域，以产生存在的材料 有用的生物线索，同时在高频处表现出较高的弹性。我们的合成策略将利用 合成聚合物化学和固态肽合成的确定多功能性以及新的 在该杂种提案中开发了正交有机化学。化学方法采用两种自然 非天然氨基酸将用于交联EMHP和RBMP，以系统地匹配机械 自然声折叠层的特性。在Christiana的临床合作者的帮助下 护理和A.I.杜邦儿童医院，将对生物活性弹性体的能力进行评估 促进声带细胞增殖，血管生成和ECM产生。这些新材料和 方法提供了有前途的路线，最终通过 活细胞，弹性支架，生物因子和机械刺激的组合。