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Lymphatic vessels, known as lymphatics, are crucial in transporting lymph from peripheral tissues to our venous system. This process begins with lymph entering through tiny capillaries that branch through tissues. These capillaries have unique features such as larger diameters, thinner walls, and a distinctive one-way valve system formed by overlapping endothelial cells.
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The vascular system comprises an extensive network of arteries, capillaries, and veins. The vascular system can be broadly divided into the blood and lymphatic systems. Typically, blood vessels can be categorized into three histological regions: tunica intima, tunica media, and tunica adventitia. The tunica intima consists of a single layer of endothelial cells attached to the basal lamina. Underlying the basal lamina is a connective tissue layer and an elastic lamina that gives stability and...
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Updated: Apr 7, 2026

Blocking Lymph Flow by Suturing Afferent Lymphatic Vessels in Mice
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Fluid Forces Control Structural Remodeling of Blind-Ended Lymphatic Microvessels.

Jacob C Holter1,2, Shashwat S Agarwal3, Joseph W Tinapple1

  • 1Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA.

Advanced Healthcare Materials
|April 6, 2026
PubMed
Summary
This summary is machine-generated.

Fluid forces significantly influence lymphatic vessel remodeling and new vessel growth (lymphangiogenesis). This study reveals how interstitial flow and vascular endothelial growth factor C (VEGF-C) drive these processes in capillary lymphatics.

Keywords:
capillary lymphaticsinterstitial fluid flowlymphangiogenesismicrofluidicsmicroscale tissue engineeringvascularized microphysiological systems

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Physiology

Background:

  • Lymphatic vessel function is critical for tissue homeostasis and is impaired in diseases like cancer.
  • Biophysical factors such as pressure and flow within the lymphatic microenvironment are altered during disease.
  • The role of fluid forces in guiding lymphatic vessel remodeling and lymphangiogenesis remains poorly understood.

Purpose of the Study:

  • To investigate how fluid forces orchestrate the remodeling of blind-ended lymphatic vessels.
  • To explore the mechanisms of lymphangiogenesis driven by microenvironmental fluid dynamics.
  • To develop a novel microphysiological system (MPS) that mimics capillary lymphatic anatomy and function.

Main Methods:

  • Development of a novel microphysiological system (MPS) to simulate interstitial, transmural, and luminal flow.
  • Utilizing the MPS to study the interplay between interstitial flow (IF) and vascular endothelial growth factor C (VEGF-C) in lymphangiogenesis.
  • Analyzing the effects of fluid forces on lymphatic vessel sprouting, cell alignment, and structural remodeling.

Main Results:

  • Interstitial flow (IF) and VEGF-C synergistically promoted lymphangiogenesis.
  • Lymphatic sprouting was most pronounced in regions of high transmural flow at the blind ends of vessels.
  • Fluid forces induced cell alignment and vessel-level phenotypic changes, including vasoconstriction and helical patterning.
  • Structural remodeling and lymphangiogenesis occurred concurrently, coordinated by endothelial cells responding to fluid forces.

Conclusions:

  • Extravascular and intraluminal endothelial cells integrate signals from native fluid forces to coordinate lymphatic vessel expansion and remodeling.
  • The developed MPS effectively recapitulates key aspects of capillary lymphatic function and response to fluid dynamics.
  • Understanding these flow-mediated mechanisms is crucial for addressing lymphatic dysfunction in disease.