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: 6869602
• 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 2006-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6869602
• 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.

贻贝粘附蛋白（MAPs）是一种重要的水下粘附性聚合物，能将海洋生物锚在其栖息的基质上。即使在有水的情况下，粘附蛋白质斑块也能与固体物体形成极其牢固的粘合，这是合成粘合剂通常无法比拟的成就。 这些蛋白质“胶”的特征在于具有高浓度的L-3，4-二羟基苯丙氨酸（DOPA），该氨基酸被认为是MAP的粘附和交联特性的原因。 然而，DOPA残基可以参与的化学反应是复杂的并且未被完全理解，特别是当它们涉及粘合和交联时。 虽然简单的整体剪切粘附力测试已经产生了重要的实践证据，表明DOPA模拟聚合物可用作粘合剂，但聚合物的设计和先前用于测量粘附力的技术对于阐明生物粘附的潜在分子方面并不理想。 因此，需要用于粘附力测试和开发下一代含DOPA的聚合物的新策略，特别是能够详细检查DOPA化学相互作用及其对粘附力的贡献的那些策略。本研究的目标是采用分子水平的粘附实验，以获得详细的了解多巴在生物粘附中的作用，并利用这些信息来激励新的含多巴的大分子生物材料的设计。新的DOPA模拟聚合物将被合成和粘合性能评估的通用断裂力学为基础的粘合测试。 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、肽组合物和底物化学之间的基本关系。 最后，将使用体外细胞毒性测定来评估对DOPA模拟聚合物的生物反应。 在这项研究的结论，我们将有相当深入的了解多巴和氧化形式的多巴在生物系统中的粘附的基本作用，并利用这些知识的合理设计的新的粘合剂生物材料。

项目成果

Biological performance of mussel-inspired adhesive in extrahepatic islet transplantation.

• DOI: 10.1016/j.biomaterials.2009.09.062
• 发表时间: 2010-01
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Brubaker, Carrie E.;Kissler, Hermann;Wang, Ling-Jia;Kaufman, Dixon B.;Messersmith, Phillip B.
• 通讯作者: Messersmith, Phillip B.

Enzymatic mineralization of hydrogels for bone tissue engineering by incorporation of alkaline phosphatase.

• DOI: 10.1002/mabi.201100501
• 发表时间: 2012-08
• 期刊: MACROMOLECULAR BIOSCIENCE
• 影响因子: 4.6
• 作者: Douglas, Timothy E. L.;Messersmith, Philip B.;Chasan, Safak;Mikos, Antonios G.;de Mulder, Eric L. W.;Dickson, Glenn;Schaubroeck, David;Balcaen, Lieve;Vanhaecke, Frank;Dubruel, Peter;Jansen, John A.;Leeuwenburgh, Sander C. G.
• 通讯作者: Leeuwenburgh, Sander C. G.

Catechol polymers for pH-responsive, targeted drug delivery to cancer cells.

• DOI: 10.1021/ja203077x
• 发表时间: 2011-08-10
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Su, Jing;Chen, Feng;Cryns, Vincent L.;Messersmith, Phillip B.
• 通讯作者: Messersmith, Phillip B.

Contact mechanics studies with the quartz crystal microbalance: origins of the contrast factor for polymer gels and solutions.

使用石英晶体微天平进行接触力学研究：聚合物凝胶和溶液的对比度因子的起源。

• DOI: 10.1021/la049015r
• 发表时间: 2004
• 期刊: Langmuir : the ACS journal of surfaces and colloids.
• 作者: Nunalee,FNelson;Shull,KennethR
• 通讯作者: Shull,KennethR

Norepinephrine: material-independent, multifunctional surface modification reagent.

去甲肾上腺素：与材料无关的多功能表面修饰试剂。

• DOI: 10.1021/ja905183k
• 发表时间: 2009-09-23
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Kang, Sung Min;Rho, Junsung;Choi, Insung S.;Messersmith, Phillip B.;Lee, Haeshin
• 通讯作者: Lee, Haeshin