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.
Work in the Laboratory is focused on the development and evaluation of novel biomaterials that can be used for drug delivery applications and as cell-delivery scaffolds in both orthopaedics and neurosurgery. Our focus has been on the development and application of in situ forming or crosslinking hydrogels formed from natural extracellular matrix molecules and polymers. Biomaterials have been developed to deliver autologous cells to the intervertebral disc, that can provide for the stiffness and biochemical cues that promote cell synthesis and phenotype. A key component of this work is the development of rational biomaterial design strategies using statistical and machine learning algorithms, in a collaboration with mathematicians at North Carolina State University. This work is supported by the NIH and North Carolina Biotechnology Center.
Inflammatory processes play a significant role in promoting pathology in diarthrodial joints, as well as intervertebral disc disorders. While protein and small molecule drugs are available to that can effectively modify the symptoms and progression of these pathologies, including the IL-1 receptor antagonist (IL1Ra) and TNF-alpha “blockers”, systemic administration can have serious side effects or be ineffective in reaching the pathological target. This has motivated our development of local drug delivery strategies to prolong drug residence time in the affected site and to decrease serum exposure. Our laboratory has developed a class of in situ forming drug depots when injected into the joint or perineural space. Conjugation of anti-inflammatory protein drugs, or anti-inflammatory small molecule compounds, is being explored and evaluated to test for increases in local residence time and bioactivity. The laboratory collaborates with chemists, rheumatologists, orthopaedic surgeons and neurosurgeons, and psychiatrists in this work to evaluate the efficacy of newly developed drug delivery strategies that act to inhibit joint inflammation and pain associated with both osteoarthritis and intervertebral disc pathologies.
Intervertebral Disc Cell Mechanobiology
Studies in the Laboratory are focused on specific cell-matrix interactions that regulate cellular synthesis and phenotype in intervertebral disc pathology. Our work has revealed the importance of environmental cues in regulating a healthy disc cell phenotype, such as physical stiffness, osmotic stimuli and oxygen tension. We have identified key extracellular matrix molecules and linking integrin isoforms as important in promoting maintenance of a biosynthetically active cells. Applications of this knowledge include the identification of novel short peptides that can replicate cell attachments to extracellular matrix proteins, the engineering of biomaterials that mimic important characteristics of disc environmental cues, and the environmental regulation of stem cell differentiation. The laboratory collaborates with rheumatologists, orthopaedic surgeons and neurosurgeons, and biomedical engineers in these studies supported by the NIH.