Biologically Inspired Polymer Adhesives

描述(由申请人提供)：贻贝黏附蛋白(MAP)是一种非凡的水下黏附聚合物，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。由于这些特性以及海洋和生理环境之间的许多相似之处，在合成聚合物中模拟MAP作为牙科和医学中的粘合剂引起了极大的兴趣。然而，由于缺乏对MAP黏附分子机制的详细了解，这些努力受到了阻碍。本研究的目的是利用纳米、微观和宏观的黏附实验，详细了解L-3，4-二羟基苯丙氨酸和其他关键残基在贻贝黏附中的黏附作用，并利用这些信息来激励以MAP为灵感的新型高分子生物材料的设计。单分子力探针测量将被用来研究DOPA和含DOPA的多肽与典型植入材料以及硬组织和软组织相互作用时的结合力和能量。为了补充单分子实验，将使用断裂微观力学方法测试水凝胶表面呈现的多肽与植入材料和组织接触所产生的粘合强度。最后，从纳米和微米尺度的黏附实验中获得的信息将被用于合理设计新的MAP模拟聚合物。这些聚合物将被合成，并作为硬组织和软组织粘合剂使用宏观范围的搭接剪切粘合强度测量进行测试。这项研究将对DOPA和其他氨基酸在生物黏附中的基础作用提供新的见解，并将产生新的黏附生物材料，用于软组织和硬组织修复、组织再生和药物输送。

DESCRIPTION (provided by applicant): 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. Because of these properties as well as many similarities between the marine and physiologic environment, there is great interest in mimicking MAPs in synthetic polymers for use as adhesives in dentistry and medicine. However, these efforts are hampered by a lack of detailed understanding of the molecular mechanism of MAP adhesion. The goals of this research are to employ nano-, micro- and macro-scale adhesion experiments to gain a detailed understanding of the adhesive role of L-3,4-dihydroxyphenylalanine (DOPA) and other key residues in mussel adhesion, and to use this information to motivate the design of new MAP-inspired macromolecular biomaterials. Single molecule force probe measurements will be performed to investigate the bond forces and energies associated with interaction of DOPA and DOPA-containing peptides with representative implant materials as well as hard and soft tissues. To complement the single molecule experiments, the adhesive strength arising from contact of ensembles of peptides presented at the surfaces of hydrogels with implant materials and tissues will be tested using a fracture micromechanics methodology. Finally, the information obtained from the nano- and micro-scale adhesion experiments will be exploited for rational design of new MAP mimetic polymers. These polymers will be synthesized and tested as hard and soft tissue adhesives using macro-scale lap shear bond strength measurements. This study will provide new insights into the fundamental role of DOPA and other amino acids in biological adhesion, and will generate new adhesive biomaterials for use in soft and hard tissue repair, tissue regeneration, and drug delivery.