PECASE: Mechanical Function of Residual Stresses in Anulus Fibrosus

9703299赛顿软骨组织，如椎间盘、关节软骨和半月板，血液供应有限，细胞密度低，因此特别容易因老化和日常磨损而退化。目前对退行性组织的治疗选择包括关节融合以防止进一步运动，或者用人工假体替换关节。然而，这些治疗方法的有效性有限，仅适用于终末期疾病的修复。迫切需要新的方法来恢复这些软骨组织的机械功能。我们的长期兴趣是开发一种组织工程方法来控制椎间盘的功能，重点是抑制或逆转进行性退变。在这个四年计划中，我们提出了一个全面的研究活动和补充教育计划，重点是生物力学和组织工程及其在椎间盘中的应用。我们的研究计划集中在研究椎间盘中的机械力-化学耦合机制，该机制通过生物化学成分影响组织功能。这种耦合机制在椎间盘纤维环中产生了肿胀引起的残余应力场和应变场，这可能在椎间盘的承载功能中起着重要作用。这项研究计划的主要目标是确定这些残余应力和应变场在纤维环中的作用，以及在具有椎间盘修复潜力的合成生物材料中的作用。激励性假说是，这些残余应力和应变通过提高其在脊柱中提供压缩负荷的能力，显著地促进了椎间盘的机械功能。一套基于残余应力、残余应变和压缩行为的设计标准将被定义为纤维环，并用于设计一种用于椎间盘组织修复的新型生物材料。拟议的研究计划围绕四个具体目标进行组织。首先，将开发新的实验方法来量化天然纤维环中的残余应变场。其次，将寻求理论模型的进步来计算天然纤维环中的残余应力场。第三，将进行实验以直接检验残余应力和应变改变纤维环的压缩承载行为的假设。第四，这些方法将被应用于评估通过工业合作提供的合成生物材料在椎间盘修复中的效用。产业界和学术界的合作团队将共同开发和评估用于恢复椎间盘机械功能的新生物材料。为高中、本科生和研究生设计了生物力学和组织工程学方面的补充教育计划。首先，将为来自少数族裔背景的二年级本科生组织实习计划。这一目标的主要目的是为了保持对本科工程教育保留率较低的学生的兴趣。其次，将修订本科生和研究生的工程课程，以扩大生物力学的课程设置。这一目标的广泛目标是为将应用研究纳入本科生和研究生水平的教育计划提供直接渠道。第三，作为杜克大学女性工程外联计划的一部分，将为高中生开发一个新的动手生物力学实验室。这一目标的广泛目标是为女高中生提供工程学方面的解决问题和建立信心的经验，并让她们接触担任领导职务的女教职员工和工程学研究生。这些研究和教育计划的结合预计将促进将工程研究转移到工业部门的伙伴关系，增加工程学中代表性不足的少数群体和妇女的数量，使这些学生更好地为在学术或工业环境中实现卓越的工程学做好准备，并使广大学生接触到工程学研究特有的发现和学习的兴奋。***

9703299 Setton Cartilaginous tissues, such as the intervertebral disc, articular cartilage and meniscus, have a limited blood supply and low cell density and so are particularly susceptible to degeneration induced by aging and daily wear. Current treatment options for degenerating tissues include fusion of the joint to prevent further motion, or replacement of the joint with an artificial prosthetic. These treatments are limited in their effectiveness, however, and are appropriate only for repair of end-stage disease. There is a great need for new methods of restoring the mechanical function in these cartilaginous tissues. Our long- term interest is in developing a tissue-engineered approach to controlling function in the intervertebral disc with a focus on inhibiting or reversing progressive degeneration. In this 4-year plan, we propose a comprehensive research activity and complementary educational program focused on biomechanics and tissue engineering with application to the intervertebral disc. Our research plan is focused on studies of a mechano-chemical coupling mechanism in the intervertebral disc which influences tissue function through biochemical composition. This coupling mechanism gives rise to swelling-induced residual stress and strain fields in the anulus fibrosus of the intervertebral disc which may be important in contributing to the load-bearing functions of the intervertebral disc. The primary objective of this research plan is to determine the function of these residual stress and strain fields in the anulus fibrosus, as well as in synthetic biomaterials with potential for disc repair. The motivating hypothesis is that these residual stresses and strains significantly contribute to the mechanical function of the intervertebral disc by improving its ability to provide for compressive load-bearing in the spine. A set of design criteria based on residual stresses, residual strains, and compressive behavior will be defined for the anulus fibrosus, and used to engineer a novel biomaterial for tissue repair in the intervertebral disc. The proposed research plan is organized about four specific aims. First, new experimental methods will be developed to quantify the residual strain fields in the native anulus fibrosus. Second, theoretical model advancements will be pursued to calculate the residual stress fields in the native anulus fibrosus. Third, experiments will be performed to directly test the hypothesis that residual stresses and strains modify the compressive load-bearing behavior of the anulus fibrosus. Fourth, these methods will be applied to evaluate synthetic biomaterials supplied through industrial collaborations for their utility in intervertebral disc repair. Teams of industrial and academic collaborators will work together to develop and evaluate new biomaterials for restoring mechanical function in the intervertebral disc. A complementary educational plan in biomechanics and tissue engineering has been designed for students at the high school, undergraduate and graduate levels. First, an internship program will be organized for second-year undergraduate students from underrepresented minority backgrounds. The broad objective of this aim is to maintain interest in a subset of students who suffer from low retention rates in the undergraduate engineering education. Second, the undergraduate and graduate engineering curriculum will be revised to expand course offerings in biomechanics. The broad objective of this aim is to provide a direct channel for incorporating applied research in educational programs at the undergraduate and graduate level. Third, a new hands-on biomechanics laboratory will be developed for high school students as part of the Women in Engineering Outreach Program at Duke. The broad objective of this aim is to provide female high school students with a problem- solving and confidence-building experience in engineering, and expose them to female faculty and engineering graduate students in leadership roles. The integration of these research and education plans is expected to promote partnerships for the transfer of engineering research to the industrial sector, to increase the numbers of underrepresented minorities and women in engineering, to better prepare these students for achieving excellence in engineering in an academic or industrial setting, and to expose a broad base of students to the excitement of discovery and learning that is characteristic of research in engineering. ***