Diffusion dynamics in the tissue: a physical model of brain clearance and cerebral edema, and cellular composition in microfluidic brain-on-a-chip platforms

Transport of small molecules in biological media is governed by microstructure, yet the quantitative link between geometry and effective diffusion remains poorly resolved, particularly for brain-on-a-chip systems. Here, we present a minimal model of brain parenchyma relevant to microfluidic systems, in which the extracellular space is treated as a porous medium with spherical cellular inclusions at prescribed volume fractions. Using finite-element simulations of steady-state Fickian transport, we have studied diffusion and tortuosity on extracellular space (ECS). We have observed essential dependence of the diffusion on the particle packing even at small volume fraction (or large ECS fraction) corresponding to those in microfluidic systems brain-on-a-chip. The results establish a direct structure-transport relationship relevant for optimizing engineering and experiments with various microfluidic physiological systems tissue-on-a-chip.