Multiscale computational model of fluid flow and matrix deformation in decellularized liver.

Currently little is known about the biomechanical environment in decellularized tissue. The goal of this research is to quantify the mechanical microenvironment in decellularized liver, for varying organ-scale perfusion conditions, using a combined experimental/computational approach. Needle-guided ultra-miniature pressure sensors were inserted into liver tissue to measure parenchymal fluid pressure ex-situ in portal vein-perfused native (n=5) and decellularized (n=7) ferret liver, for flow rates from 3-12mL/min. Pressures were also recorded at the inlet near the portal vein cannula to estimate total vascular resistance of the specimens. Experimental results were fit to a multiscale computational model to simulate perfusion conditions inside native versus decellularized livers for four experimental flow rates. The multiscale model consists of two parts: an organ-scale electrical analog model of liver hemodynamics and a tissue-scale model that predicts pore fluid pressure, pore fluid velocity, and solid matrix stress and deformation throughout the 3D hepatic lobule. Distinct models were created for native versus decellularized liver. Results show that vascular resistance decreases by 82% as a result of decellularization. The hydraulic conductivity of the decellularized liver lobule, a measure of tissue permeability, was 5.6 times that of native liver. For the four flow rates studied, mean fluid pressures in the decellularized lobule were 0.6-2.4mmHg, mean fluid velocities were 211-767μm/s, and average solid matrix principal strains were 1.7-6.1%. In the future this modeling platform can be used to guide the optimization of perfusion seeding and conditioning strategies for decellularized scaffolds in liver bioengineering.