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. ***
