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

Abstract

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 3–12 mL/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 to 2.4 mmHg, mean fluid velocities were 211 to 767 µm/s, and average solid matrix principal strains were 1.7 to 6.1%. In future this modeling platform can be used to guide the optimization of perfusion seeding and conditioning strategies for decellularized scaffolds in liver bioengineering.

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

“…Please see Appendix-Mathematical modeling of liver biology and metastases, and cancer mechanobiology in the Supplementary Materials for an expanded overview of the prior work. Briefly, there is a rich history of mathematical modeling of liver biology, particularly liver tissue regeneration [18,19], liver fibrosis [20,21], liver toxicology [22,23], interstitial flow and mechanics in liver tissues [24][25][26][27][28][29][30]. Others have modeled the role of tissue mechanics on (mostly primary) tumor growth [31][32][33][34], including some excellent work on the role of mechanosensing in individual tumor cell proliferation [35,36], although these did not focus specifically on primary or metastatic tumor growth in liver tissues.…”

“…A detailed mathematical description of the mechanics of poroviscoelastic materials was published by [86], and the application of poroviscoelastic models to liver tissue has been demonstrated by [87][88][89] among others. The summary given here is adapted from [29,89,90]. A biphasic material consists of a linear elastic solid phase and an incompressible fluid phase, where relative motion between the two phases produces rate-dependent (i.e.…”

“…In order to model the liver microenvironment, a three-dimensional poroviscoelastic finite element model of a quarter liver lobule ( Fig. 11) was created in Abaqus (v6.12, 3DS Dassault Systems, Waltham, MA), modified from the prior work of Nishii et al [29]. A poroviscoelastic material model was selected because this constitutive description of liver tissue mechanics has been shown to capture the viscoelastic stress-strain behavior of the solid matrix as well as pressure-driven flow of fluid through the matrix pores [29].…”

Flow dynamics analyses of pathophysiological liver lobules using porous media theory

“…The 3D hexagonal model of a liver lobule employed in the current work ( Fig. 1a) was directly adopted from the literature [19,26], since the geometric dimensions used for modeling liver lobules and the corresponding tracts or vessels have been discussed extensively in those works. Here the lobule was simplified as a hexagonal prism with six cylinders at the ridges to mimic its PTs, and a central cylinder at the center to replicate its CV, both of which serve as the channels for blood flow.…”

“…The height of the regular hexagonal prism H = 0.5 mm, and the circumradius of its cross section R L = 0.25 mm. The cylinders located on the six ridges were set as PTs with radius R PT = 0.02 mm, and the central cylinder was set as CV with radius R CV = 0.03 mm [19,26]. The grey zone between the PTs and the CV represents the liver sinusoidal network ( Fig.…”