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: 8266386
• 负责人: Dominic Edward Fullenkamp
• 金额: $ 4.72万
• 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/8266386
• 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; tissue repair; 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）：贻贝足丝将贻贝拴在海洋中的岩石上，并承受类似于血管系统中所经历的循环应力。心脏不断泵送血液，对血管壁和瓣膜施加压力；海浪不断冲击海岸，对连接贻贝和岩石的细线施加压力。有趣的是，这些螺纹当应变超过屈服点时，会表现出恢复机械性能的时间依赖性能力。这种自我修复特性归因于贻贝线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的单个金属离子周围配位。这些配位键需要比共价键更小的力来破坏，作为线的最薄弱的环节。据信，这些键以时间相关的方式重新形成，导致股丝的杨氏模量部分恢复。以足丝的分子结构为灵感，我们建议通过将金属结合肽序列纳入材料的聚合物主链来开发自修复材料。具体来说，我们计划开发基于聚乙二醇的水凝胶，该水凝胶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。同时，我们计划使用单分子力谱来了解贻贝足丝的分子基础和材料的自愈特性。我们相信单分子实验将深入了解大块材料的机械性能，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；没有任何合成材料被证明是小血管移植的理想选择。自修复生物材料将是血管组织替代品的理想选择，与目前的合成聚合物不同，它具有机械稳定性。目前，尚不存在适合小血管移植物（例如冠状动脉搭桥中使用的血管移植物）的理想合成材料。公众健康相关性：对于那些没有合适的移植物（通常来自腿部静脉）的患者，仅存在质量较差的替代品。我们建议开发具有自愈能力的材料，其灵感来自于贻贝足丝，并且可能被证明是小血管的良好组织替代品。