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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 大自然设计的最引人注目的机械装置之一由两个小折叠组成 称为声带的组织，负责在发声时产生多种声音 受到气管气流的振动。正常情况下，声带可承受高达 30% 的应变 频率为 100 至 1000 Hz。然而，过度的机械应力和有害的病理 某些情况可能会对这个脆弱的系统造成损害，导致广泛的声带疾病。到 迄今为止，声带疾病的最佳治疗方法尚未实现，组织工程方法 有望实现功能性声带的再生。然而，独特的生化成分， 声带的结构组织和粘弹性具有非常复杂的组织 利用传统聚合生物材料的工程工作。 在这项新的合作努力中，我们整合了初级和早期职业教师的独特专业知识， 将生产新型生物活性弹性体，可用作声带组织的有益支架 工程。这些生物材料将捕捉分子结构和机械特性 天然弹性蛋白（弹性蛋白和节肢弹性蛋白）；鉴于这两种物质不同的理化性质 蛋白质，同时采用两者将提供一种综合方法来调整形态、机械和 新材料的生物学特性。弹性蛋白模拟杂化聚合物（EMHP）将包含 多嵌段结构，具有交替的疏水性、弹性合成结构域和亲水性、基于肽的结构域 交叉链接域。合成块预计将表现出类似橡胶的弹性，从而在功能上发挥作用 模仿弹性蛋白弹性域的特性，而肽域将服务于结构 和生物学功能。此外，基于节肢弹性蛋白的模块化多肽（RBMP）将通过以下方法生产： 独特功能模块的多次重复，包括基于节肢弹性蛋白的肽结构域、肝素结合 肽、细胞粘附肽和 MMP 敏感结构域，以生产呈现 有用的生物线索，同时在高频下表现出高弹性。我们的合成策略将利用 合成高分子化学和固态肽合成的既定多功能性，以及新的 COBRE 提案中开发了正交有机化学。化学方法采用天然 非天然氨基酸将用于交联 EMHP 和 RBMP，以系统地匹配机械性能 特性与自然声带固有层的特性相同。在克里斯蒂娜临床合作者的帮助下 护理和人工智能杜邦儿童医院将评估生物活性弹性体的能力 促进声带细胞增殖、血管生成和 ECM 产生。这些新材料和 方法提供了通过以下方法最终设计功能性声带固有层的有前途的途径 活细胞、弹性支架、生物因素和机械刺激的组合。