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

该奖项是根据2009年《美国复苏和再投资法案》(公法111-5)资助的。“研究工作：由于在这种界面上形成的高水平局部应力，附着不同材料是一项重大的工程挑战。这个问题的有效生物解决方案可以在肌腱的附着处看到(顺从的、结构性的软组织？)到骨(僵硬的、结构性的、硬的组织？)。存在于未受伤的肌腱和骨之间的独特的过渡组织在愈合过程中不会被重建，因此手术重新附着这两种不同的生物材料经常失败。我们建议对肌腱到骨的植入进行反向工程，以指导合成和生物衍生梯度材料的开发。将探索两个项目：区域1：功能梯度生物材料中的应力传递机制。其具体目的是通过研究肌腱-骨界面(一种功能梯度生物材料)的力学性能，(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来确定应力传递的机制。其具体目标是利用胶原基质和细胞合成功能梯度生物材料。我们寻求通过分级来实现机械性能的分级：(1)生物矿物和(2)纤维软骨。教育努力：拟议的教育活动旨在向从小学到研究生院的所有级别的学生介绍生物力学。将以肩袖肌腱到骨的植入部位为平台，向所有学生展示功能梯度材料的概念。未来五年，国际生物工程学会将参与的教育活动的具体目标是：(1)向小学生介绍生物力学，(2)激励女中学生进入理工科职业生涯，(3)教育社会了解力学原理如何支撑肩袖损伤和修复的生理结果，(4)向本科生和工程专业研究生传授分级生物材料的概念，以及(5)让本科生和研究生接触与生物分级材料有关的研究课题。这项研究将通过将一个既定的概念(即分级材料)引入一个新的领域(即生物医学工程)来推动该领域的发展。这将导致对梯度生物材料的更好理解，并将导致功能梯度材料的合成。国际和平协会发表了17篇论文(总共26篇)，并在该地区获得了大量赠款。此外，他亦获颁冯永祥青年调查员奖，以表扬他的工作。此外，他利用现有资源进行了初步实验和计算，以表明他的所有想法都可以在该计划的5年课程内实现。BROADER影响：研究/教育计划的耦合将(1)让所有级别的学生接触生物力学概念，(2)让工程学学生接触生物学中分级材料的概念。教育活动将产生广泛的影响，针对包括小学生、女中学生和社区在内的多个人群。这项研究将有助于理解生物附着体上负载转移的机制，并将这一知识应用于合成功能梯度矩阵。这些知识将对医学应用(例如，加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)产生直接影响。

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).