On-chip engineered human lymphatic microvasculature for physio-/pathological transport phenomena studies

The human vasculature constitutes an integral part of fluid, protein and cellular transport throughout a variety of physiological processes and pathological events. While the blood vascular system has been the topic of numerous studies in connection to its role in physio-/pathological transport phenomena, our secondary vascular system, the lymphatics, has yet to gain similar attention, in part due to a lack of adequate models to study its biological function. Despite their considerable value, animal models limit the ability to perform parametric studies, whereas current in vitro systems are lacking in physiological mimicry. Here, a microfluidic-based approach is developed that allows for precise control over the transport of growth factors and interstitial fluid flow, which we leverage to recapitulate the in vivo growth of lymphatic capillaries. Using this approach, physiological tissue functionality is validated by characterizing the drainage rate of extracellular solutes and proteins. Finally, lymphatic-immune interactions are studied to affirm inflammation-driven responses by the lymphatics, which recruit immune cells via chemotactic signals, similarly to in vivo , pathological events. Results demonstrate the utility of this platform to study lymphatic biology and disease, as well as use as a screening assay to predict lymphatic absorption of therapeutic biologics. ### Competing Interest Statement R.D.K. is a cofounder of AIM Biotech that markets microfluidic systems for 3D cell culture. R.D.K. also receives research support from Amgen, Roche, Boeringer Ingelheim, Glaxo-Smith-Kline, and AbbVie.