Immobilisation of Lactate Oxidase and Deoxyribonuclease I for use within a Bio-Artificial Liver Assist Device for the Treatment of Acute Liver Failure

摘要: Constraints of cell supply indicate that proliferating lines are likely to be essential components Bio-Artificial Liver support devices (BAL) for the treatment acute liver failure. The Group BAL employs clones cells derived from HepG2 line, which in common with many tumour cells, predominantly dependent on anaerobic glycolysis energy supply, leading production lactate within bioreactor. system requires prolonged culture alginate encapsulated and accumulation presents a potential hazard this system: at ~15 mM, accumulated becomes toxic bioreactor, also compromises bead integrity by chelating calcium ions necessary polymerisation. Furthermore, lineage could prove threat patient safety should any DNA enter patient’s system. It was hypothesised inclusion immobilised Lactate oxidase (LOx) catalyse degradation into pyruvate offset these limitations whilst simultaneously providing source utilisable cells. In similar fashion, Deoxyribonuclease I (DNase I) utilised remove non-patient during phase Here it is demonstrated functionalised glass beads feasible method immobilising LOx DNase I. Enzymatic activity retained even after incubation 37°C presence human plasma, offering means reducing levels culture, potentially removing circulating below practically detectable levels, thus facilitating cellular performance efficiency as safe effective therapy