Modeling transport in physiologically realistic tumor microenvironment*

We present a first principles model for perfusion in tumor extracellular matrix (ECM), with realistic morphology. Our study conducts high-fidelity Eulerian multiphase simulations of blood flow in both idealized and imaging-based tumor vessels and numerically tracks the subsequent intratumoral plasma transport. The tumor vessel simulations enforce pulsatile flow, treating red and white blood cells and plasma as distinct phases under viscous-laminar transient conditions. We also incorporate glycocalyx patches along luminal vessel surfaces and the resulting electrohydrodynamic effects. Using plasma flux data from intra-vessel simulations at endothelial gaps, we next model plasma penetration into the ECM, bearing physiologically feasible interstitial pressure and fiber packing. The derived perfusion trends are compared with our analytical convection-diffusion model. The results indicate an inverse correlation between plasma percolation rates and intratumoral diffusion distances, validated by experiments in a millimeter-scale 3D-printed ECM topology and microfluidic chambers with ECM-mimicking collagen gel. In the latter, our model predicts mechanical response trends in the ECM domain during pulsed droplet motion through adjoining vessels.