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

Mohammad Mehedi Hasan Akash^1,2*Mohammad Yeasin²Shima Mahmoudirad³Redowan A Niloy⁴Jiyan Mohammad⁵Katie Reindl⁵Anupam Pandey³Saikat Basu^2*

• ¹FAMU-FSU College of Engineering, Tallahassee, United States
• ²South Dakota State University, Brookings, United States
• ³Syracuse University, Syracuse, United States
• ⁴University of Notre Dame, Notre Dame, United States
• ⁵North Dakota State University, Fargo, United States

ABSTRACT 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 integrationed of numerical computationscomputational 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 towith a calibrated reverse advection-diffusion (RAD) model for intratumoral plasma transport. The reduced-order tumor microenvironment model usesincorporates glycocalyx-patch on the luminal surface as an electrohydrodynamic (EHD) force at the tumor vessel wall via glycocalyx patches on the luminal surface. Akash et al. 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 25.34%). Numerical simulations of plasma perfusion in both the tumor ECM domain and a microfluidic benchmark exhibit two-stage kinetics, with an initial advection-dominated regime. The RAD model reproduces this behavior and, aftera simple temporal calibration, to account for pore-scale hydrodynamic acceleration resolved by computational fluid dynamics (CFD),matches the observed propagation. 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 tissue 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.