Reduced-order modeling of solute transport within physiologically realistic solid tumor microenvironment.

Introduction: Solid tumors are characterized by densely packed extracellular matrices and limited vascularization, creating significant resistance to both diffusive and convective transport. Tumor growth depends on complex flow-structure interactions across multiple scales, while vascular abnormalities and enhanced permeability elevate interstitial pressure in the tumor microenvironment. Methods: In this study, we developed an integrated computational framework with a theoretical modeling framework that couples three phase, viscous-laminar, transient simulations of glycocalyx-patched tumor vessel-resolving plasma, red blood cells (RBCs), and white blood cells (WBCs) and tracking their volume fractions with a calibrated reverse advection-diffusion (RAD) model for intratumoral plasma transport. The reduced-order tumor microenvironment model incorporates electrohydrodynamic (EHD) force at the tumor vessel wall via glycocalyx patches on the luminal surface. Results: At the fenestra, EHD increases inlet plasma intensity relative to a non-EHD framework across all 15 numerical models (means: 0.576 non-EHD vs. 0.722 EHD; gain Discussion: By using fully resolved, EHD-inclusive multiphase CFD simulations to calibrate a reduced-order RAD model parameterized by measurable geometric features, we bridge the gap between classical Darcy-Starling perfusion models and fully resolved CFD. The resulting framework provides a tractable mechanism-grounded tool for quantifying plasma progression in dense solid tumors and for establishing the baseline transport capacity of the tumor extracellular matrix, independent of solute-specific biochemical properties.