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

0844607科普普洛斯该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助。“研究工作：不同材料的连接是一个主要的工程挑战，因为在这样的界面处会产生高水平的局部应力。 一个有效的生物解决方案，这个问题可以看到在附着的肌腱（一个顺应性，结构？软组织？）骨（僵硬，结构？硬组织？）。未受伤肌腱和骨之间存在的独特过渡组织在愈合过程中不会重新生成，因此这两种不同生物材料的手术重新连接通常会失败。我们建议对肌腱-骨插入进行逆向工程，以指导合成和生物衍生梯度材料的开发。将探讨两个项目：区域1：功能梯度生物材料中的应力传递机制。具体目标是通过研究以下方面的分级来确定肌腱-骨界面（功能梯度生物材料）处的应力传递机制：（1）机械性能，（2）纤维软骨含量，和（3）在微米和纳米尺度下的矿物质含量和结构。区域2：功能梯度生物材料的组织工程。具体目标是使用胶原基质和细胞合成功能梯度生物材料。通过（1）生物矿物质和（2）纤维软骨的分级，实现力学性能的分级。教育工作：建议的教育活动旨在向从小学到研究生院的各级学生介绍生物力学。肩袖肌腱-骨插入部位将作为一个平台，向所有学生介绍功能梯度材料的概念。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）鼓励女中学生进入科学和工程领域，（3）教育社区了解力学原理如何成为肩袖损伤和修复的生理结果的基础，（4）向本科生和研究生讲授梯度生物材料的概念;（5）让本科生和研究生接触与梯度生物材料相关的研究课题。智力优势：PI致力于推进功能梯度生物材料的知识。这项研究将通过引入一个既定的概念（即，梯度材料）到新的领域（即，生物医学工程）。这将导致更好地理解梯度生物材料，并将导致功能梯度材料的合成。PI发表了17篇论文（共26篇），并在该领域获得了许多赠款。他还获得了Y.C.冯扬研究员奖，以表彰他的工作。此外，他还利用现有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5年的课程中实现。更广泛的重要性：结合研究/教育的建议将（1）让各级学生接触生物力学概念，（2）让工程专业的学生接触生物学中的分级材料概念。教育活动将针对包括小学生、女中学生和社区在内的多种人群产生广泛影响。这项研究将导致了解的机制，帮助转移负载在生物附件和应用这些知识的功能梯度矩阵的合成。这些知识将对医疗应用产生直接影响（例如，以增强腱-骨愈合）以及工程应用（例如，设计更好的飞机机翼附件）。

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).