Evaluation of a single-use Bioartificial Liver (BAL) biocartridge consisting of cryopreservable alginate encapsulated liver cell spheroids as a component of HepatiCan TM , a novel Bioartificial Liver device

Eloy Erro¹Tom Brookshaw¹Barry Fuller²Sweta Chandel¹Joana Mendonca da Silva¹Elizaveta Zotova¹Sherri-Ann Chalmers¹Alfie Watt¹Clare Selden^1*

• ¹Institute for Liver and Digestive Health, University College London, London, England, United Kingdom
• ²Division of Surgery and Interventional Science, Faculty of Medical Sciences, University College London, London, England, United Kingdom

Alternative therapies to complement liver transplantation and treat patients with liver failure are not available. In this study, a clinical scale single-use biocartridge was developed for use as part of a novel Bioartificial Liver device (HepatiCan TM ), utilising conditioned human-derived alginate encapsulated liver spheroids (AELS), within a fluidised bed. To develop the optimal biocartridge, two designs (B2 and B3) were created and modelled to best replicate the performance of our pre-existing reusable cartridge (B1). The suitability of designs, and their ability to deliver the required hydrodynamic conditions for AELS, during both spheroid production and treatment phases, was addressed by computational fluid dynamics. The main difference between the designs (B2 and B3) was the base plate flow distributor. Preserving the hole pattern in the base plate, between B1 and B3, was critical for mimicking fluid flow. Additionally, increasing the number of orifices in the cross-patterned base plate design (B3) provided further benefits: maintaining homogeneity in fluid velocity distribution, whilst avoiding "dead-flow" zones. Hence, the final biocartridge design (B3) was as effective in fluid distribution as the original (B1). B3 surpassed B1 in velocity uniformity over the first 10mm above the base plate, critical for good mass-transfer between biomass and perfusing fluid in the fluidised bed.