Engineering approaches to investigate the roles of lymphatics vessels in rheumatoid arthritis

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory joint disorders. While our understanding of the autoimmune processes that lead to synovial degradation has improved, a majority of patients are still resistant to current treatments and require new therapeutics. An understudied and promising area for therapy involves the roles of lymphatic vessels (LVs) in RA progression, which has been observed to have a significant effect on mediating chronic inflammation. RA disease progression has been shown to correlate with dramatic changes in LV structure and interstitial fluid drainage, manifesting in the retention of distinct immune cell phenotypes within the synovium. Advances in dynamic imaging technologies have demonstrated that LVs in RA undergo an initial expansion phase of increased LVs and abnormal contractions followed by a collapsed phase of reduced lymphatic function and immune cell clearance in vivo. However, current animal models of RA fail to decouple biological and biophysical factors that might be responsible for this lymphatic dysfunction in RA, and a few attempted in vitro models of the synovium in RA have not yet included the contributions from the LVs. Various methods of replicating LVs in vitro have been developed to study lymphatic biology, but these have yet not been integrated into the RA context. This review discusses the roles of LVs in RA and the current engineering approaches to improve our understanding of lymphatic pathophysiology in RA.