2019 Otto Schmitt Lecture (Setton) | Institute for Engineering in Medicine Archives

"The Death and Re-Birth of the Intervertebral Disc Cell"

11:50am–12:50pm
Tuesday, October 29, 2019
Moos Tower, Room 2-620

Abstract

Intervertebral disc disorders contribute to pain and disability in millions of affected individuals annually, such that low back pain and neck pain are ranked #1 and #4 for disease impact globally. Microenvironmental conditions for resident cells of the intervertebral disc contribute to an early decrease in cellularity, and associated loss of intervertebral disc height, loss of hydration, tissue destruction and eventual disc collapse or herniation. The most vulnerable of disc cells are the nucleus pulposus cells, derived from embryonic notochord, that are distinct from the neighboring mesenchymal cells that form the anulus fibrosus. Our laboratory has studied the micromechanical environment of these nucleus pulposus cells and factors that regulate nucleus pulposus cell phenotype and biosynthesis. We have demonstrated an ability to promote biosynthesis and survival through modulation of cell-matrix interactions with a focus on presenting key peptides and proteins that replicate some features of notochordal development. We have also advanced knowledge of environmental cues that promote a healthy, biosynthetically active nucleus pulposus cell, and identified mechanobiology strategies to restore a healthy phenotype for pathological, human primary disc cells. This talk will review an understanding of the micromechanical environment and mechanobiology of the disc cells, and our work with engineering substrates and protein-conjugated biomaterials to promote matrix regeneration, cell differentiation and consequently cell “re-birth” in the intervertebral disc.

BIOGRAPHY

Dr. Setton received her B.S.E. from Princeton University in Mechanical and Aerospace Engineering, with M.S. and Ph.D. degrees in Mechanical Engineering from Columbia University. Dr. Setton joined the Department of Biomedical Engineering at Duke University in 1994, where she served as the Bevan Distinguished Professor of Biomedical Engineering and Orthopaedic Surgery. Dr. Setton recently joined the Department of Biomedical Engineering at Washington University to accept the position as Lopata Distinguished Professor of Biomedical Engineering & Orthopaedic Surgery.

Dr. Setton’s research focuses on understanding the mechanisms for degeneration and regeneration of soft tissues of the musculoskeletal system. Recent work focuses on development of in situ forming hydrogels for drug delivery and tissue regeneration in the knee joints and spine. She has funded her lab through grants from the NIH, NSF, Whitaker Foundation, Coulter Foundation, OREF, AO Foundation, and North Carolina Biotechnology Center and research agreements with many corporations.

Dr. Setton has over 170 peer-reviewed publications and has licensed several patents for commercial development. She has served on the Editorial Advisory Boards of the Annual Reviews of Biomedical Engineering, Journal of Biomechanical Engineering, Osteoarthritis and Cartilage, and Journal of Biomechanics. She has also served on the Boards of the Orthopaedic Research Society, World Council on Biomechanics, and as President of the Biomedical Engineering Society. Dr. Setton is a Fellow of the ASME, BMES and AIMBE, and has received a PECASE Award, Dean’s Award for Outstanding Research, Graduate Dean’s Award for Excellence in Mentoring, and ASME’s Mow Medal.