Engineering tissues for autonomous, mechanically-activated drug delivery

Engineering biological tissues to replace the degenerated tissues present in chronic diseases is a promising strategy for restoring healthy physiology. Within the musculoskeletal system, chronic diseases are exacerbated by aberrant mechanical forces.  In an effort to develop engineered cartilage tissues that autonomously drive therapeutic drug release based on applied mechanical force, I investigated the role of the mechanosensitive ion channel transient receptor potential vanilloid 4 (TRPV4) in engineered cartilage. By bridging finite element models with cellular mechanobiological assays, I identified the mechanical mechanisms that activate TRPV4 in engineered cartilage tissues. Mapping the transcriptomic landscape downstream to TRPV4 activation opened a number of distinct TRPV4-dependent targets for therapeutic intervention. By co-opting these targets within synthetic gene circuits, I could engineer cartilage tissues that respond to mechanical loading to drive anti-inflammatory biologic drug production. This “mechanogenetic” approach has applications for both therapeutic development across a number of disease systems as well as for developing tools which identify how mechanical forces drive chronic diseases.

Dr. Nims is a Research Instructor at Washington University in St. Louis. He received his B.S. in Biomedical Engineering at Boston University and his Ph.D. in Biomedical Engineering from Columbia University. He received a National Research Service Award during his postdoctoral training and was awarded a New Investigator Recognition Award from the Orthopedic Research Society.

His research focuses on engineering therapeutic tissues for treating chronic musculoskeletal diseases. His work deconstructs mechanobiological pathways and re-engineers the cellular signals to drive synthetic drug delivery. He has co-authored 26 peer-reviewed journal articles and is a co-inventor on two patent applications of engineered therapies for restoring the osteoarthritic joint environment.

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