Research in the Laboratory is focused on understanding the mechanisms for degeneration and regeneration of soft tissues of the musculoskeletal system, including the intervertebral disc, articular cartilage, and meniscus.

Cartilage Mechanobiology

Studies in the Laboratory are focused on specific cell-matrix interactions in controlling cellular synthesis and phenotype that may contribute to joint pathology in osteoarthritis and intervertebral disc degeneration. Systems to mechanically load isolated cells, cell-gel constructs and tissues in vitro are used, along with highly resolved visualization systems, to determine the means by which cells interact their local environment. Modern techniques in molecular and cell biology are used in combination with engineering analysis to determine relevant physical stimuli and to identify new regulators of the associated cellular responses. The laboratory collaborates with Virginia B. Kraus of Rheumatology, Farshid Guilak and William J. Richardson of Orthopaedic Surgery, Tod Laursen of Civil and Environmental Engineering, and Mansoor Haider of North Carolina State University in these studies supported by the NIH.

Tissue Engineering

Work in the Laboratory is focused on the development and evaluation of novel biomaterials that can be used for drug delivery applications in orthopaedics and neurosurgery, and for promoting regeneration of soft tissues. Recent work has focused on in situ forming or crosslinking polypeptide hydrogels, in a collaboration with Ashutosh Chilkoti of BME. The laboratory collaborates with rheumatologists and orthopaedic surgeons and neurosurgeons to evaluate the feasibility of drug delivery strategies to inhibit joint inflammation. In addition, the Laboratory collaborates with surgeons and materials scientists to evaluate scaffolds that assist in functional tissue repair. A key component of this work is the development of rational biomaterial design strategies using statistical and machine learning algorithms, in a collaboration with Mansoor Haider of North Carolina State University . This work is supported by the NIH, North Carolina Biotechnology Center and research sponsors.

Collagen Mutations and Extracellular Matrix Mechanics

Mutations in genes for proteins of the cartilage extracellular matrix have been associated with premature onset of osteoarthritis or disc degeneration in humans and animal models. Work in the Laboratory is focused on determining the mechanisms by which collagen mutations give rise to joint degeneration through combined studies of functional and behavioral phenotyping, studies of extracellular matrix mechanics, anatomical characterizations, and studies of cellular metabolism. Collagen mutations are associated with changes in extracellular matrix stiffness in cartilage tissues characteristic of osteoarthritis, but also generate substantial changes in bone morphology, cell metabolism and viability, and the expression of inflammatory factors and matrix-degrading proteases, each of which may contribute to premature onset of joint degeneration. This work forms the basis for one project of a 5-year NIH-funded Program Project led by Dr. Farshid Guilak. In this work, the Setton Laboratory collaborates with Drs. Tim Griffin of Orthopaedic Surgery and Virginia Kraus of Rheumatology. Other investigators dedicated to the study of Biomechanics and Inflammation in Osteoarthritis are Drs. Frank Keefe of Psychiatry, David Pisetsky of Rheumatology and Brice Weinberg of Hematology/Oncology.