Probing interstitial fLUid hoMEostasis with an Organ on Chip platform to investigate solute transport in tissues – PLUME_2

Tissue homeostasis depends on the coordinated functions of blood and lymphatic vessels, along with connective tissues, to regulate the absorption and drainage of nutrients, gases, hormones, and cellular waste. While the Starling principle has long served as a model for solute transport, the dynamics of interstitial fluid transport remain a topic of debate. To address this challenge, we introduce PLUME, an innovative organ-on-chip platform designed for real-time measurement and analysis of interstitial fluid and solute transport under biomimetic conditions.
PLUME is structured into three work packages (WPs). The first WP focuses on tissue bioengineering and instrumentation to develop the organ-on-chip platform. PLUME integrates a parallel network of blood and lymphatic microvessels within a biomimetic geometry, along with a module for biomimetic pressure actuation. A key innovation is its novel, probe-free instrument for real-time interstitial fluid flow measurement, leveraging the physics of poroelasticity.
The second WP is dedicated to fabricating a biomimetic supporting tissue using a self-assembly process that generates a complex and rich in proteins extracellular matrix. This tissue will undergo structural, biochemical, and biophysical characterization to create a shared, annotated database of biomimetic biomaterials. Additionally, we will assess the functional properties of blood and lymphatic endothelial cells within these engineered tissues.
The final WP explores colloidal transport — particularly extracellular vesicle dynamics — within PLUME under normal and pathological conditions, including altered mechanical actuation and diseased tissues. This experimental work will be complemented by finite element transport models based on poroelastic principles, enabling us to dissect the regulatory mechanisms of interstitial flow and their dysfunction in disease states.
By integrating advanced tissue engineering with cutting-edge technologies, PLUME aims to refine classical models of tissue transport, deepen our understanding of homeostatic processes, and provide a scientific foundation for optimizing drug delivery following blood administration.