Intervertebral disc biology and pain

Intervertebral disc (IVD) degeneration greatly contributes to low back pain; how the IVD generates this pain remains unclear. The Setton Lab images sensory neuron activation in pre-clinical models of IVD degeneration by recording Ca2+-sensitive fluorescence indicators. In collaboration with the Tang Lab, this work studies temporal and spatial changes in behavior and sensitivity, neuronal function and innervation patterns, hemodynamics of brain activity, and how their crosstalk changes in the degenerated IVD.

Intra-articular drug delivery

Pathologies such as osteoarthritis and rheumatoid arthritis reduce diarthrodial joint function and quality of life. Although proteins and small molecule drugs can alleviate symptoms and disease progression, their systemic administration poses serious side effects and may not reach the target site. This motivates our work to prolong drug residence time and bioactivity in health and disease. We are currently studying drug transport through the synovium, a multi-layered connective tissue whose capillaries and lymphatic vessels clear both small and large molecules from the joint space. We coupled experimental data with computational models to show that solute size affects diffusivity in synovial explants. This approach can predict factors that regulate intra-articular drug transport. The Setton Lab has also developed injectable drug carriers for intra-articular delivery that increase particle size and residence time in the joint space.

Intervertebral disc cells and regeneration

The Setton lab has studied cell-matrix interactions that regulate cellular synthesis and phenotype in intervertebral disc (IVD) pathology. Our work has shown that environmental cues, such as physical stiffness and attachment ligands, regulate healthy disc cell phenotype. We apply this knowledge to design biomaterials that mimic key environmental cues for primary disc cells and progenitor cells. Injectable biomaterial carriers are used to deliver cells that restore the degenerated IVD.