Mussel-inspired self-healing hydrogels for vascular tissue repair

受贻贝启发的自愈水凝胶用于血管组织修复

• 批准号: 8066720
• 负责人: Dominic Edward Fullenkamp
• 金额: $ 4.68万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8066720
• 关键词: Adhesives; Architecture; Behavior; Binding; Biocompatible Materials; Biological Models; Biology; Blood Vessels; Breathing; Cessation of life; Collagen; Collagen Fibril; Coronary Artery Bypass; Development; Drug Delivery Systems; Engineering; Environment; Evolution; Face; Failure; Fatigue; Future; Health; Heart; Heart Valves; Histidine; Hydrogels; Individual; Inferior; Ions; Leg; Link; Marines; Mechanical Stress; Mechanics; Mediating; Medical; Metals; Molecular; Morbidity - disease rate; Mussels; Oceans; Patients; Polyethylene Glycols; Polymers; Process; Property; Prunella vulgaris; Resistance; Rupture; Spectrum Analysis; Stress; Stretching; Structure; System; Time; Tissue Adhesives; Tissues; Vascular System; Veins; Vertebral column; Wound Healing; base; blood pump; byssal threads; clinically relevant; covalent bond; design; experience; improved; insight; man; mortality; novel; operation; partial recovery; protein aminoacid sequence; research study; scaffold; single molecule; tool

DESCRIPTION (provided by applicant): The mussel byssal thread tethers mussels to rocks in the ocean and is subjected to cyclic stresses similar to those experienced in the vascular system. The heart continuously pumps blood, stressing vessel walls and valves; ocean waves continuously hit the shore, stressing the threads attaching mussels to rocks. Interestingly, these threads, when strained beyond their yield point, show a time-dependent ability to recover their mechanical properties. This self-healing property has been attributed to the high histidine content at the ends of mussel thread collagen. It is believed that multiple histidines coordinate around single metal ions at the ends of the collagen fibrils. These coordination bonds require less force to break than covalent bonds, serving as the weakest links of the thread. In a time-dependent manner these bonds are believed to reform, resulting in the partial recovery of the Young's modulus of the byssal thread. Using the molecular architecture of the byssal thread as inspiration, we propose to develop self-healing materials by incorporating metal-binding peptide sequences into the material's polymer backbone. Specifically, we plan to develop polyethylene glycol-based hydrogels, which have been investigated for many medical applications, including tissue adhesives, cellular scaffolds, and drug-delivery systems. Concurrently, we plan to develop an understanding of the molecular basis of the mussel byssal threads and the material's self- healing properties, using single-molecule force spectroscopy. We believe single-molecule experiments will provide insight into the bulk material mechanical properties and provide guidance for future material design. Robust materials are needed to stand up to the harsh environment of the vascular system; no synthetic materials have been shown to be ideal for small vessel grafts. Self-healing biomaterials would be ideal for vascular tissue replacements, providing mechanical stability unlike current synthetic polymers. Currently, no synthetic materials exist that are ideal for small vessel grafts such as those used in coronary artery bypass. PUBLIC HEALTH RELEVANCE: For those patients who do not have suitable grafts (usually from veins in the leg), only inferior quality substitutes exist. We propose to develop materials that have the ability to self-heal, which are inspired by the mussel byssal thread, and may prove to be good tissue replacements for small vessels.

描述（由申请人提供）：贻贝深海线将贻贝拴在海洋中的岩石上，并受到类似于脉管系统所经历的循环应力。心脏不断地泵血，给血管壁和瓣膜施加压力;海浪不断地撞击海岸，给贻贝和岩石之间的连接线施加压力。有趣的是，这些线，当应变超过其屈服点，显示出时间依赖的能力，以恢复其机械性能。这种自我修复的特性归因于贻贝丝胶原蛋白末端的高组氨酸含量。据信，多个组氨酸在胶原原纤维末端处围绕单个金属离子配位。这些配位键比共价键需要更小的力来断裂，作为线的最弱连接。在一个时间依赖的方式，这些债券被认为是改革，导致部分恢复的杨氏模量的深渊线程。利用深渊线的分子结构作为灵感，我们建议通过将金属结合肽序列纳入材料的聚合物骨架来开发自我修复材料。具体来说，我们计划开发聚乙二醇基水凝胶，它已被研究用于许多医疗应用，包括组织粘合剂，细胞支架和药物输送系统。与此同时，我们计划利用单分子力光谱学来了解贻贝深海丝的分子基础和材料的自我修复特性。我们相信，单分子实验将提供深入了解块体材料的力学性能，并为未来的材料设计提供指导。需要坚固的材料来承受血管系统的恶劣环境;没有合成材料被证明是小血管移植物的理想选择。自愈合生物材料将是理想的血管组织替代品，提供机械稳定性，不像目前的合成聚合物。目前，还没有合成材料可以理想地用于小血管移植物，例如用于冠状动脉搭桥术的材料。公共卫生相关性：对于那些没有合适的移植物（通常来自腿部静脉）的患者，只有劣质的替代品存在。我们建议开发具有自我愈合能力的材料，其灵感来自贻贝深海线，并且可能被证明是小血管的良好组织替代品。