A CARRIER-MEDIATED TRANSPORT OF TOXINS IN A HYBRID MEMBRANE - SAFETY BARRIER BETWEEN A PATIENTS BLOOD AND A BIOARTIFICIAL LIVER

Combination of detoxifying liver support systems with liver cell biore actors may have additional benefits for the treatment of liver failure due to the replacement of known and unknown metabolic activities of t he liver. However, the problem of side effects and possible risks caus ed by the use of animal hepatocytes or hepatoma cells remains unsolved which underlines the need of a safety barrier between the patients bl ood and the extracorporeal bioreactor. Passive filters do not meet the requirements of such membranes, because in liver failure desired and undesired molecules in the patients blood share similar physicochemica l properties. That challanges the developement of biologically designe d separation membranes. A hybrid membrane is formed by implementation of transport proteins into a highly permeable hollow fiber. The transp ort of free solutes and albumin bound toxins is tested in vitro in com parison with conventional high flux membranes. The transport character istics for tightly albumin bound toxins are significantly improved for the hybrid membrane. The transport of albumin bound toxins across the membrane is not associated with albumin. The selectivity of the trans port is evaluated in vivo. No significant loss of middle molecular wei ght hormones attached to other carrier proteins was observed. Neither transport of immunologically relevant proteins across the membrane nor loss of valuable proteins was measured. Also in vivo, a significant r eduction of protein bound toxins and a transport of metabolically rele vant solutes, like amino acids, was shown. The presented hybrid membra ne may be used like an ''intellegent membrane'' as a safety barrier be tween the patients blood and cell devices.