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Annual Review of Biomedical Engineering

Volume 27, 2025

Understanding the Lymphatic System: Tissue-on-Chip Modeling

  • William J. Polacheck1,2,3, J. Brandon Dixon4,5,6 and Wen Yih Aw1
  • 1Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill and Raleigh, North Carolina, USA; email: [email protected] 2Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA 3McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA 4Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA 5George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA 6Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA
  • Vol. 27:73-100 (Volume publication date May 2025)
  • First published as a Review in Advance on January 22, 2025
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

The lymphatic vasculature plays critical roles in maintaining fluid homeostasis, transporting lipid, and facilitating immune surveillance. A growing body of work has identified lymphatic dysfunction as contributing to the severity of myriad diseases and to systemic inflammation, as well as modulating drug responses. Here, we review efforts to reconstruct lymphatic vessels in vitro toward establishing humanized, functional models to advance understanding of lymphatic biology and pathophysiology. We first review lymphatic endothelial cell biology and the biophysical lymphatic microenvironment, with a focus on features that are unique to the lymphatics and that have been used as design parameters for lymphatic-on-chip devices. We then discuss the state of the art for recapitulating lymphatic function in vitro, and we acknowledge limitations and challenges to current approaches. Finally, we discuss opportunities and the need for further development of microphysiological lymphatic systems to bridge the gap in model systems between lymphatic cell culture and animal physiology.

Keyword(s): lymphatic-on-chip, lymphatics, mechanobiology, microphysiological systems, organs-on-chip
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2025-05-01
2025-06-15
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/content/journals/10.1146/annurev-bioeng-110222-100246
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Understanding the Lymphatic System: Tissue-on-Chip Modeling
Annual Review of Biomedical Engineering 27, 73 (2025); https://doi.org/10.1146/annurev-bioeng-110222-100246
/content/journals/10.1146/annurev-bioeng-110222-100246
/content/journals/10.1146/annurev-bioeng-110222-100246
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