Evaluation of parenchymal fluid pressure in native and decellularized liver tissue

One strategy for tissue engineering of bioartificial livers is the use of decellularized liver scaffolds, which contain a functional vascular network and intact extracellular matrix components. Due to the known mechanosensitivity of liver cells, particularly the response of hepatocytes to changes in parenchymal fluid pressure (PFP), it is necessary to evaluate the biomechanical environment within decellularized scaffolds. The objective of this study was to characterize the dependence of PFP on perfusion flow rate, in native and decellularized liver. Needle-guided Millar SPR-524 (3.5F) pressure sensors were inserted into liver parenchyma to measure PFP in-situ in rat (n=5) and ex-situ in portal vein-perfused native (n=5) and decellularized (n=7) liver tissue. Average in-situ PFP, measured in the left, central and right lobes, was found to be 2.86±1.04 mmHg. PFP measured in ex-situ liver perfused at 3, 6, 9, and 12 ml/min was found to increase linearly with flow rate. Decellularized liver PFP ranged from 0.68 mmHg at 3ml/min to 2.42 mmHg at 12 ml/min, while native liver ranged from 4.32 – 11.93 mmHg. Results demonstrate that PFP in decellularized scaffolds can be controlled by varying flow rate. These results will be implemented in a poroviscoelastic finite element model of liver perfusion, developed by the authors, to predict PFP distribution in three-dimensional scaffolds for known flow rates. This computationally efficient model can be used to optimize perfusion bioreactor conditions throughout the scaffold, to aid in the engineering of functional liver tissue from a decellularized liver organoid.