CAREER: Functionally graded biologic materials- tissue engineering of the tendon-to-bone insertion

职业：功能分级生物材料——肌腱-骨插入的组织工程

• 批准号: 0844607
• 负责人: Stavros Thomopoulos
• 金额: $ 40万
• 依托单位: Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0844607&HistoricalAwards=false
• 关键词: CAREER; Functionally; graded; biologic; materials

0844607ThomopoulosThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."RESEARCH EFFORT: The attachment of dissimilar materials is a major engineering challenge because of the high levels of localized stress that develop at such interfaces. An effective biologic solution to thisproblem can be seen at the attachment of tendon (a compliant, structural ?soft tissue?) to bone (a stiff,structural ?hard tissue?). The unique transitional tissue that exists between uninjured tendon and bone is not recreated during healing, so surgical reattachment of these two dissimilar biologic materials often fails. We propose to reverse engineer the tendon-to-bone insertion to guide development of synthetic and biologically-derived graded materials. Two projects will be explored:Area 1: Mechanisms of stress transfer in functionally graded biologic materials. The specific aim is to determine the mechanisms for stress transfer at the tendon-to-bone interface (a functionally graded biologic material) by studying the gradation in: (1) mechanical properties, (2) fibrocartilage content, and (3) mineral content and structure at the micro- and nano- scales.Area 2: Tissue engineering of functionally graded biologic materials. The specific aim is to synthesize functionally graded biologic materials using collagen matrices and cells. We seek to achieve a gradation in mechanical properties through gradations in: (1) bio-mineral, and (2) fibrocartilage.EDUCATIONAL EFFORT: The proposed educational activities are designed to introduce biomechanics to students at all levels, from elementary school to graduate school. The rotator cuff tendon-to-bone insertion site will be used as a platform to present the concept of functionally graded materials to all students. The educational activities in which the PI will participate over the next five years have the specific goals of: (1) introducing biomechanics to elementary school students, (2) inspiring female middle school students to enter careers in science and engineering, (3) educating the community on how mechanics principles underlie the physiologic outcomes in rotator cuff injury and repair, (4) teaching the concept of graded biologic materials to undergraduate and graduate engineering students, and (5) exposing undergraduate and graduate students to research topics related to graded biologic materials.INTELLECTUAL MERIT: The PI seeks to advance the knowledge of functionally graded biologic materials. The research will advance the field by introducing an established concept (i.e., graded materials) to a new field (i.e., biomedical engineering). This will result in a better understanding of graded biologic materials and will lead to the synthesis of functionally graded materials. The PI has published 17 papers (out of a total of 26) and received numerous grants in the area. He has also received the Y.C. Fung Young Investigator award in recognition of his work. In addition, he has performed pilot experiments and calculations using available resources to show that all of his ideas are achievable within the 5-year course of the proposal.BROADER IMPACTS: The coupled research/education proposal will (1) expose students at all levels to biomechanics concepts, and (2) expose engineering students to the concept of graded materials in biology. Educational activities will have a broad impact by targeting multiple populations, including elementary school students, female middle school students, and the community. The research will lead to an understanding of the mechanisms which aid transfer of load at biologic attachments and to an application of this knowledge for synthesis of functionally graded matrices. This knowledge will have a direct impact in medical applications (e.g., to enhance tendon-to-bone healing) as well as engineering applications (e.g., to design better airplane wing attachments).

0844607Thomopoulos 该奖项根据 2009 年美国复苏和再投资法案（公法 111-5）提供资金。“研究工作：不同材料的附着是一项重大的工程挑战，因为在此类界面处会产生高水平的局部应力。针对此问题的有效生物解决方案可以在肌腱（顺应性的结构性“软组织”）与骨骼（a僵硬的、结构性的 ？硬组织？）。未受伤的肌腱和骨骼之间存在的独特的过渡组织在愈合过程中不会重建，因此这两种不同的生物材料的手术重新附着通常会失败。我们建议对肌腱到骨骼的插入进行逆向工程，以指导合成和生物衍生的分级材料的开发。将探索两个项目：领域1：功能分级生物制剂中的应力传递机制 材料。具体目标是通过研究以下方面的梯度来确定肌腱与骨界面（功能梯度生物材料）的应力传递机制：（1）机械性能，（2）纤维软骨含量，以及（3）微米和纳米尺度的矿物质含量和结构。领域2：功能梯度生物材料的组织工程。具体目标是合成功能分级的生物制剂 使用胶原蛋白基质和细胞的材料。我们力求通过以下方面实现机械性能的分级：(1) 生物矿物质和 (2) 纤维软骨。 教育工作：拟议的教育活动旨在向从小学到研究生的各个级别的学生介绍生物力学。肩袖肌腱到骨骼的插入部位将用作向所有学生展示功能分级材料概念的平台。的 PI 将在未来五年内参与的教育活动具有以下具体目标：(1) 向小学生介绍生物力学，(2) 激励女中学生进入科学和工程领域的职业生涯，(3) 教育社区了解力学原理如何构成肩袖损伤和修复的生理结果，(4) 向工程本科生和研究生教授分级生物材料的概念，以及 (5) 让本科生和研究生接触与分级生物材料相关的研究主题。智力价值：PI 致力于增进功能分级生物材料的知识。该研究将通过将既定概念（即分级材料）引入新领域（即生物医学工程）来推进该领域的发展。这将有助于更好地理解分级生物材料，并导致功能性生物材料的合成 分级材料。该 PI 发表了 17 篇论文（总共 26 篇），并获得了该领域的大量资助。他还获得了 Y.C.冯杨研究员奖以表彰他的工作。此外，他还利用可用资源进行了试点实验和计算，以表明他的所有想法都可以在该提案的 5 年课程内实现。 更广泛的影响：耦合的研究/教育提案将 (1) 让各个级别的学生接触到 生物力学概念，(2) 让工程专业的学生了解生物学中分级材料的概念。教育活动将针对小学生、女中学生和社区等多种人群，产生广泛的影响。该研究将有助于了解有助于生物附件负载转移的机制，并将这些知识应用于合成功能分级基质。这些知识将对医疗应用产生直接影响（例如， 增强肌腱到骨骼的愈合）以及工程应用（例如，设计更好的飞机机翼附件）。