Mechanically active extracellular matrix fibers for tissue engineering applications

项目总结/摘要 组织固有地与它们周围的基质机械地相互作用，但是组织工程材料没有 充分利用这种相互作用来增强与人体的融合。此外，只有少数材料具有 已经开发出允许通过机械力控制药物递送的方法，并且现有方法使用 组织整合潜力有限的合成聚合物或使用机械强度弱的水凝胶。的 该研究计划的目标是开发机械活性和可调的细胞外基质蛋白纤维， 利用机械-生物化学特性控制心血管组织工程中的细胞行为 应用.该研究计划提出开发一种新的材料，可以改善长期 通过递送生物活性分子来促进血管移植物的开放性， 机械刺激，同时比合成聚合物更容易与组织整合。力学性能 将通过改变材料的成分来调整。不同组成的细胞外基质纤维将被 通过湿纺产生，并使用定制和Instron在潮湿和干燥状态下进行机械测试 拉伸试验机这将使我们能够确定蛋白质含量和机械性能之间的关系 如模量、强度和韧性，以产生具有特定性能的纤维。新型机械敏感型 细胞外基质蛋白及其配体之间的相互作用，以及这些相互作用的影响 对细胞行为和信号传导的影响。为了做到这一点，细胞外基质纤维将被拉伸并结合 通过免疫染色观察蛋白质对纤维的影响。确定的相互作用可能是新的 细胞检测其环境的机制。蛋白质工程将用于 产生治疗性蛋白质，所述治疗性蛋白质响应于限定的机械作用而从细胞外基质纤维释放， 刺激，这可以促进材料的内皮化。这种材料可以用来增强组织 整合和改善血管移植物的长期结果。完成这个项目将有助于申请人 实现她的职业目标，成为一个领先的工业研究人员，因为批判性思维， 实验设计和新的技术技能，她将获得细胞信号，细胞行为和蛋白质 工程.申请人还将通过提高沟通技巧来改善其职业轨迹， 通过撰写研究论文、出席会议和研讨会并在会上发言， 还有经营期刊俱乐部波士顿大学生物医学中心的支持和协作环境 工程部门，以及申办者、共同申办者和 合作者，将帮助申请人成功完成培训和研究计划。

Project Summary/Abstract Tissues inherently interact mechanically with their surrounding matrix, but tissue engineering materials have not fully exploited this interaction to enhance integration with the human body. Moreover, only a few materials have been developed that allow control of drug delivery through mechanical forces, and existing methods use synthetic polymers which have limited potential for tissue integration or use mechanically weak hydrogels. The goal of the research plan is to develop mechanically active and tunable fibers of extracellular matrix proteins that leverage mechano-biochemical properties to control cell behavior in cardiovascular tissue engineering applications. The research plan proposes to develop a new class of materials that could improve long-term patency of vascular grafts by delivering bioactive molecules that encourage endothelialization in response to mechanical stimuli, while integrating with tissues more easily than synthetic polymers. The mechanical properties of the material will be tuned by altering the composition. Extracellular matrix fibers of varied compositions will be generated through wet spinning and mechanically tested in a wet and dry state using custom-built and Instron tensile testers. This will allow us to determine the relationship between protein content and mechanical properties like modulus, strength, and toughness in order to generate fibers with specific properties. New mechanosensitive interactions between extracellular matrix proteins and their ligands, as well as the impact of these interactions on cell behavior and signaling will be identified. To do this, extracellular matrix fibers will be stretched and binding of proteins to the fibers will be observed through immunostaining. The interactions identified could be new mechanisms through which cell detect the mechanics of their environment. Protein engineering will be used to generate therapeutic proteins that release from extracellular matrix fibers in response to defined mechanical stimuli, which could promote endothelialization of the material. The material could be used to enhance tissue integration and improve long term outcomes in vascular grafts. Completing this project will help the applicant achieve her career goals of becoming a leading industrial researcher because of the critical thinking, experimental design, and new technical skills she will gain in cell signaling, cell behavior, and protein engineering. The applicant will also improve her career trajectory by enhancing her communication skills and conceptual knowledge through writing research papers, attending and presenting at conferences and seminars, and running journal clubs. The supportive and collaborative environment of the Boston University Biomedical Engineering department, as well as the relevant expert knowledge of her Sponsor, Co-sponsor, and collaborators, will help the applicant successfully complete the training and research plans.