CAREER: Engineering Functional Muscle-Tendon Structures using Scaffold-Free Cell-Based Directed Assembly and Theoretical Modeling

职业：使用无支架、基于细胞的定向组装和理论建模来工程功能性肌肉肌腱结构

• 批准号: 0954990
• 负责人: David Corr
• 金额: $ 45万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0954990&HistoricalAwards=false
• 关键词: CAREER; Engineering; Functional; Muscle; Tendon

0954990CorrThis integrated research and education CAREER proposal is focused to understand the role of fiber network architecture on overall tissue function, and thus establish the structure-function relationship. In the PI's scaffold-free approach, the natural ability of cells to grow and create their own extracellular matrix is harnessed, using geometric constraint, to form functional single fibers. This bottom-up approach will be utilized to create and tune fibers that will serve as building blocks for muscle-tendon structures, in which the architecture can be specified to fiber-level precision. The mechanical characterization of these muscle-tendon structures, when coupled with fiber-based theoretical modeling, will provide insight required to establish the structure-function relationship.The key novelties to this approach are: (1) scaffold-free engineering and mechanical evaluation of single fibers formed by directed cell growth, and (2) building functional muscle-tendon structures to precise fiber-level architecture. This represents a fundamental shift in tissue engineering approach; one necessary to create functional muscle-tendon units in which both muscle and tendon fiber architecture dictate the physiological and biomechanical function of the structure. This research program will utilize a scaffold-free approach to engineer muscle and tendon fibers by directing the growth of myoblasts and fibroblasts using geometric constraints to: (1) develop a fundamental understanding of the influence of environmental stimuli on cellular growth and fiber formation, in both muscle and tendon. (2) determine set(s) of bioreactor parameters for optimal muscle and tendon fiber performance(3) characterize the influence of fiber and crimp geometry on crimped engineered tendon fibers viscoelastic low-load and failure properties, using theoretical modeling and experimentation. (4) create functional muscle-tendon structures with fiber-level architectural fidelity to achieve the desired mechanical performance, as guided by theoretical modeling simulations.(5) establish the structure-function relationship for engineered muscle-tendon structures; including the contributions of each tissue, and compatibility at the muscle-tendon interface.The research will be complemented by integrated educational projects at the graduate, undergraduate and K-12 academic levels, both within Rensselaer Polytechnic Institute and as educational outreach. The latest research findings and methods will be incorporated into 3 graduate/undergraduate hybrid courses currently taught or co-taught by the PI, and a related 5-week lab experiment will be developed for the Cell & Tissue Engineering track of the Biomedical Engineering Laboratory course. Tissue engineering knowledge gained will be integrated into the PI's ongoing undergraduate (BIR Workshop) and K-12 (Design Your Future Day) outreach seminars. Furthermore, the PI will introduce a week-long biomaterials module into the summer American Society of Materials "Materials Day Camp", using an interactive series of hands-on experiments to establish the structure-function relationship of collagen networks present in soft tissues.

0954990 Corr这一综合研究和教育的职业生涯建议的重点是了解纤维网络结构对整体组织功能的作用，从而建立结构-功能关系。 在PI的无支架方法中，利用细胞生长和产生自身细胞外基质的天然能力，使用几何约束，形成功能性单纤维。 这种自下而上的方法将用于创建和调整纤维，这些纤维将作为肌肉肌腱结构的构建块，其中可以将架构指定为纤维级精度。 这些肌肉-肌腱结构的力学特性，结合基于纤维的理论建模，将提供建立结构-功能关系所需的洞察力。这种方法的关键创新点是：（1）定向细胞生长形成的单纤维的无支架工程和力学评估，以及（2）构建功能性肌肉-肌腱结构以精确的纤维水平架构。 这代表了组织工程方法的根本转变;一个必要的创造功能性肌肉肌腱单位，其中肌肉和肌腱纤维结构决定了结构的生理和生物力学功能。该研究计划将利用无支架方法，通过使用几何约束指导成肌细胞和成纤维细胞的生长来工程化肌肉和肌腱纤维，以：（1）对环境刺激对肌肉和肌腱中细胞生长和纤维形成的影响进行基本了解。(2)确定用于最佳肌肉和肌腱纤维性能的生物反应器参数组（3）使用理论建模和实验表征纤维和卷曲几何形状对卷曲工程化肌腱纤维粘弹性低负荷和失效性质的影响。(4)在理论建模仿真的指导下，创建具有纤维级架构保真度的功能性肌肉肌腱结构，以实现所需的机械性能。(5)建立工程化肌肉肌腱结构的结构-功能关系;包括每个组织的贡献，以及肌肉肌腱界面的兼容性。该研究将通过研究生，本科生和K-12学术水平的综合教育项目进行补充，无论是在伦斯勒理工学院还是作为教育推广。 最新的研究成果和方法将被纳入目前由PI教授或共同教授的3门研究生/本科生混合课程，并将为生物医学工程实验室课程的细胞组织工程轨道开发一个相关的5周实验室实验。 获得的组织工程知识将被整合到PI正在进行的本科（BIR研讨会）和K-12（设计你的未来日）外展研讨会。 此外，PI将在美国材料学会夏季“材料日营”中引入为期一周的生物材料模块，使用一系列互动的动手实验来建立软组织中胶原蛋白网络的结构-功能关系。