Mechanically active extracellular matrix fibers for tissue engineering applications

用于组织工程应用的机械活性细胞外基质纤维

基本信息

批准号：
9910682
负责人：
Gwendolyn Ann Hoffmann
金额：
$ 3.62万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-13 至 2023-06-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9910682
关键词：
Arterial Fatty Streak Arteries Behavior Binding Binding Proteins Binding Sites Biochemical Biological Biomedical Engineering Boston Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cell Differentiation process Cells Chimeric Proteins Collagen Communication Communities Critical Thinking Custom Development Drug Controls Drug Delivery Systems Endothelial Cells Endothelium Engineering Environment Experimental Designs Extracellular Matrix Extracellular Matrix Proteins Fiber Fibronectins Fluorescence Goals Growth Factor Human body Hydration status Hydrogels Implant Industrialization Intervention Journals Knowledge Laminin Learning Ligands Literature Mechanics Membrane Methods Minor Modeling Modulus Nidogen Outcome Paper Pathology Physiological Polymers Process Property Protein Engineering Protein Fragment Proteins Research Research Personnel Role Running Signal Transduction Silk Site Stains Stimulus Stress Stretching Technical Expertise Techniques Tenascin Testing Time Tissue Engineering Tissues Training Universities Vascular Graft Vascular Patency Writing base career cell behavior collaborative environment design experience experimental study flexibility improved improved outcome interest learning materials mechanical force mechanical properties migration novel optical fiber physical property protein function response scaffold skills supportive environment symposium therapeutic protein tool

项目摘要

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.

项目概要/摘要组织本质上与其周围基质发生机械相互作用，但组织工程材料却没有充分利用这种相互作用来增强与人体的融合。而且，只有少数材料具有已开发出允许通过机械力控制药物输送的技术，并且使用现有方法组织整合潜力有限的合成聚合物或使用机械性能较弱的水凝胶。这该研究计划的目标是开发细胞外基质蛋白的机械活性和可调纤维利用机械生化特性来控制心血管组织工程中的细胞行为应用程序。该研究计划提出开发一种可以改善长期效果的新型材料通过提供生物活性分子促进内皮化以响应血管移植物的通畅机械刺激，同时比合成聚合物更容易与组织结合。机械性能材料的性能将通过改变成分来调整。不同成分的细胞外基质纤维将通过湿纺产生，并使用定制和 Instron 在湿和干状态下进行机械测试拉力测试仪。这将使我们能够确定蛋白质含量和机械性能之间的关系例如模量、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将确定对细胞行为和信号传导的影响。为此，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机制的机制。蛋白质工程将用于产生治疗性蛋白质，这些蛋白质响应特定的机械作用从细胞外基质纤维中释放刺激，可以促进材料的内皮化。该材料可用于增强组织整合并改善血管移植物的长期结果。完成该项目将有助于申请人由于批判性思维，她实现了成为领先工业研究员的职业目标，她将在细胞信号传导、细胞行为和蛋白质方面获得实验设计和新技术技能工程。申请人还将通过提高沟通技巧和能力来改善她的职业轨迹通过撰写研究论文、参加会议和研讨会并在会上发表演讲来获取概念知识，和经营期刊俱乐部。波士顿大学生物医学学院的支持和协作环境工程部门，以及其赞助商、联合赞助商和合作伙伴的相关专业知识合作者，将帮助申请人顺利完成培训和研究计划。