No abstract

Acute and acute-on-chronic liver failure are associated to high mortality when transplantation is not possible. The lack of donors has resulted in an important demand for liver support devices. This paper describes the design and validation of a new bioartificial liver (BAL) device including fluidized bed bioreactors hosting alginate-encapsulated hepatocytes spheroids. To ensure the efficacy of the BAL and the safety of the patients, a complex extracorporeal circulation was designed to be compatible with a commercial medical device, the Prismaflex(®) monitor, already used in intensive care units. Preclinical studies on large animal show that the treatment was well tolerated in terms of hemodynamics considerations. A method using non adhesive coating in petri dish led to the production of large amount of viable spheroids in vitro that were further encapsulated to follow up bioartificial liver activity during four days.

Increasing bead density clearly maintained the performances of the fluidized bed with plasma of different compositions, without any risk of release out of the bioreactor. A 1% (v/v)-concentration of microspheres in alginate solution did not result in any alteration of the mechanical or biological behavior. This concentration can thus be applied to the production of large-scale encapsulated biomass for further use of the Suppliver setup in human scale preclinical studies.