Bioadhesive Polymer Hydrogels: Basic and Applied Studies

贻贝黏附蛋白(MAP)是一种引人注目的水下黏附聚合物，它能形成坚韧的键，将海洋生物固定在它们栖息的基质上。即使在水存在的情况下，粘性蛋白斑块也能与固体物体形成极其坚韧的结合，这一成就通常是合成粘合剂无法比拟的。这些蛋白质“胶”的特征是含有高浓度的L-3，4-二羟基苯丙氨酸，这是一种被认为与MAP的粘连和交联性有关的氨基酸。然而，DOPA残基参与的化学反应是复杂的，还没有完全了解，特别是当它们与粘合和交联有关时。尽管简单的整体剪切粘附性测试已经产生了重要的实用证据，表明模拟DOPA的聚合物可以用作粘合剂，但聚合物的设计和以前用于测量粘附性的技术对于阐明生物粘附性的潜在分子方面并不理想。因此，需要新的粘合测试策略和开发下一代含DOPA的聚合物，特别是那些能够详细检查DOPA的化学作用及其对粘合的贡献的策略。本研究的目的是利用分子水平的黏附实验来详细了解DOPA在生物黏附中的作用，并利用这些信息来推动含有DOPA的新型高分子生物材料的设计。将合成新的模拟DOPA的聚合物，并通过基于通用断裂力学的粘合测试来评估粘合性能。通过对DOPA化学反应的现场控制，将揭示粘接性能与DOPA含量、DOPA氧化、多肽组成和底物化学之间的基本关系。最后，将使用体外细胞毒性测试来评估DOPA模拟聚合物的生物反应。在本研究的结论中，我们将深入了解DOPA和氧化形式的DOPA在生物系统中对黏附的基本作用，并利用这些知识来合理设计新的黏附生物材料。

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.