Mussel-inspired self-healing hydrogels for vascular tissue repair

描述(申请人提供)：贻贝在海洋中将贻贝系在岩石上，承受与血管系统相似的循环压力。心脏持续泵血，使血管壁和瓣膜承受压力；海浪不断冲击海岸，使贻贝与岩石相连的丝线受到压力。有趣的是，当超过屈服点时，这些线显示出恢复其机械性能的时间依赖能力。这种自愈特性归因于贻贝丝胶原蛋白末端的高组氨酸含量。据认为，多个组氨酸围绕胶原纤维末端的单个金属离子进行配位。与共价键相比，这些配位键需要的断裂力量较小，是这条线中最薄弱的一环。以一种依赖时间的方式，这些键被认为是改革的，导致部分恢复的杨氏模数的字节线。受骨链的分子结构启发，我们建议通过将金属结合肽序列引入材料的聚合物骨架来开发自我修复材料。具体地说，我们计划开发基于聚乙二醇基的水凝胶，这种水凝胶已经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，我们计划利用单分子力谱来了解贻贝丝线的分子基础和材料的自我修复特性。我们相信，单分子实验将提供对块体材料力学性质的洞察，并为未来的材料设计提供指导。需要坚固的材料来抵抗血管系统的恶劣环境；还没有合成材料被证明是小血管移植物的理想材料。自我修复生物材料将是血管组织替代的理想材料，与目前的合成聚合物不同，它提供了机械稳定性。目前，还没有合成材料可以理想地用于小血管移植物，如用于冠状动脉搭桥的移植物。公共卫生相关性：对于那些没有合适的移植物(通常是来自腿部静脉的移植物)的患者，只有劣质替代品存在。我们建议开发具有自我修复能力的材料，这种材料的灵感来自贻贝的背部线条，可能被证明是小血管的良好组织替代品。

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.