Bioadhesive Polymer Hydrogels: Basic and Applied Studies

生物粘附聚合物水凝胶：基础和应用研究

• 批准号: 6718381
• 负责人: Phillip B Messersmith
• 金额: $ 28.13万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6718381
• 关键词: aminoacid analyzer; biomaterial development /preparation; biomimetics; biotechnology; cell adhesion molecules; chemical bond; crosslink; cytotoxicity; dihydroxyphenylalanine; electrochemistry; gel; guinea pigs; high performance liquid chromatography; mass spectrometry; metal oxide; oxidation; polymers; protein sequence; surface property; viscosity

Mussel adhesive proteins (MAPs) are remarkable underwater adhesive polymers that form tenacious bonds to anchor marine organisms onto the substrates upon which they reside. Even in the presence of water, the adhesive protein plaques form extremely tenacious bonds to solid objects, an accomplishment which is not often matched by synthetic adhesives. These protein 'glues' can be characterized as having a high concentration of L- 3,4-dihydroxyphenylalanine (DOPA), an amino acid that is believed to be responsible for both adhesive and crosslinking characteristics of MAPs. However, the chemical reactions in which DOPA residues can participate are complex and not fully understood, particularly as they relate to adhesion and crosslinking. Although simple bulk shear adhesion tests have yielded important practical evidence that DOPA-mimetic polymers may be useful as adhesives, the design of the polymers and the techniques that were previously used for measuring adhesion are not ideal for elucidating the underlying molecular aspects of bioadhesion. Thus, new strategies for adhesion testing and the development of the next generation of DOPA-containing polymers are needed, in particular those that enable detailed examination of DOPA chemical interactions and their contribution to adhesion. The goals of this research are to employ molecular-level adhesion experiments to gain a detailed understanding of the role of DOPA in biological adhesion, and to use this information to motivate the design of new DOPA-containing macromolecular biomaterials. New DOPA-mimetic polymers will be synthesized and adhesive properties assessed by a versatile fracture mechanics based adhesion test. In-situ control of DOPA chemical reactions will be used to reveal fundamental relationships between adhesive performance and DOPA content, DOPA oxidation, peptide composition, and substrate chemistry. Finally, an in vitro cytotoxicity assay will be used to assess the biological response to the DOPA-mimetic polymers. At the conclusion of this study we will have gained considerable insight into the fundamental role of DOPA and oxidized forms of DOPA on adhesion in biological systems, and utilized this knowledge for the rational design of new adhesive biomaterials.

贻贝黏附蛋白（map）是一种非凡的水下黏附聚合物，可以形成牢固的键，将海洋生物固定在它们所居住的底物上。即使在有水的情况下，粘附蛋白斑块也能与固体物体形成极其牢固的结合，这是合成粘合剂通常无法比拟的。这些蛋白质“胶”的特点是具有高浓度的L- 3,4-二羟基苯丙氨酸（DOPA），这种氨基酸被认为是MAPs的粘合和交联特性的原因。然而，多巴残基参与的化学反应是复杂的，尚未完全了解，特别是与粘附和交联有关的化学反应。虽然简单的体剪切黏附试验已经产生了重要的实际证据，证明模仿多巴胺的聚合物可能是有用的黏附剂，但聚合物的设计和以前用于测量黏附的技术对于阐明生物黏附的潜在分子方面并不理想。因此，需要新的粘附测试策略和开发下一代含有DOPA的聚合物，特别是那些能够详细检查DOPA化学相互作用及其对粘附的贡献的策略。本研究的目的是通过分子水平的粘附实验来详细了解DOPA在生物粘附中的作用，并利用这些信息来激励新型含DOPA的大分子生物材料的设计。将合成新的dopa模拟聚合物，并通过基于断裂力学的粘合测试来评估粘合性能。DOPA化学反应的原位控制将用于揭示粘合剂性能与DOPA含量、DOPA氧化、肽组成和底物化学之间的基本关系。最后，体外细胞毒性试验将用于评估对多巴模拟聚合物的生物反应。在这项研究的结论中，我们将对DOPA和DOPA的氧化形式在生物系统中粘附的基本作用有了相当大的了解，并利用这些知识来合理设计新的粘附生物材料。