Bioengineering a cryogel-derived bioartificial liver using particle image velocimetry defined fluid dynamics

Bioartificial Liver (BAL) devices are extracorporeal systems designed to support or recover hepatic function in patients with liver failure. The design of an effective BAL remains an open challenge since it requires a complex co-optimisation of cell colonisation, biomaterial scaffold and BAL fluid dynamics. Building on previous evidence of suitability as a blood perfusion device for detoxification, the current study investigated the use of RGD-containing p(HEMA)-alginate cryogels as BAL scaffolds. Cryogels were modified with alginate to reduce protein fouling and functionalised with an RGD-containing peptide to increase hepatocyte adhesion. A novel approach for characterisation of the internal flow through the porous matrix was developed by employing Particle Image Velocimetry (PIV) to visualise flow inside cryogels. Based on PIV results, which showed the laminar nature of flow inside cryogel pores, a multi-layered bioreactor composed of spaced cryogel discs was designed to improve blood/hepatocyte mass exchange. The stacked bioreactor showed a significantly higher production of albumin and urea compared to the column version, with improved cell colonisation and proliferation over time. The cell-free cryogel-based device was tested for safety in a bile-duct ligation model of liver cirrhosis. Thus, a stacked bioreactor prototype was developed based on a surface-engineered cryogel design with optimised fluid dynamics for BAL use.