Download Biomaterial development for adsorption technologies used in acute

Biomaterial development for adsorption technologies used in acute liver
failure and multiorgan-failure therapy
D.Falkenhagen, M.Brandl, M.Ettenauer, J.Hartmann and V.Weber
Department of Clinical Medicine and Biotechnology
Danube University Krems, Krems, Austria
Introduction: Acute liver failure and multiorgan-failure are very complex diseases involving
not only metabolic parameters but also coagulation- and complement factors as well as
different mediators of the cytokine network. Therefore, therapy of acute liver failure (ALF)
and multiorgan-failure (MOF) are of high complexicity involving intensive care measures as
well as special therapies such as extracorporeal blood purification methods. Especially in
acute liver failure extracorporeal blood purification techniques aiming pathophysiologically
relevant toxins are in clinical use such as the so-called MARSR – technology as well as the
PrometheusR system which was originally developed as the first prototype in Krems. A
similar system containing 3 very specific adsorption-columns for the removal of the cytokine
IL-6, endotoxins and the complement factor C5a in series has been developed for MOFtreatment by the company “adexter” in Germany.
Those systems are based on combined membrane-adsorbent techniques containing
conventional adsorption systems based on columns filled with particles made from different
polymers or activated charcoal being able to adsorb ALF or MOF-relevant substances having
a particle size of 200-800 µm.
Method: A new technique – the MDS (Microspheres Based Detoxification Systems) has been
developed by our team that uses micro and nanoparticles for adsorption in suspension and not
in columns. Those micro- and nanoparticles are used as a mixture of different adsorbent
structures specifically modified for adsorption of different substances being important in ALF
and MOF. The suspension of micro- and/or nanoparticles is integrated part of the filtrate
compartment of a hollow fiber membrane filter whose sieving coefficient can vary from a
molecular weight of 100.000 (for ALF) to 2.000.000 (for MOF). For safety reasons a highly
intelligent optical sensor based on the detection of magnetically fluorescent marker
microparticles is integrated in the blood circuit in order to detect adsorbent particles in case of
a rupture of the hollow fiber membranes in the filter before entering the blood circuit of the
patient treated.
Results: The new technology has several advantages such as high efficiency due to very large
external and internal surface areas of the micro- and nanoparticles and high flexibility due to
the possibility to use several adsorbents in combination or in sequence. The MDS offers a 1020 time higher efficiency in comparison to conventional adsorption methods described earlier.
The adsorbents used in MDS are now designed for the therapy of ALF being able to remove
especially protein-bound substances such bilirubin, bile acids, aromatic amino acids, phenols
etc but also endotoxins, complement factors such as C5a and Cytokines such as TNF.
Conclusion: Newly developed biomaterials for extracorporeal membrane- but especially
adsorption technologies are on the way to improve significantly therapeutic possibilities of
ALF and MOF – therapy considering the complexicity of those diseases.