Functionalization and Application of Cellulose Microparticles as Adsorbents in Extracorporeal Blood Purification

Abstract

Therapeutic apheresis is established as supportive therapy for various diseases, such as hypercholesterolemia, autoimmune diseases, liver failure, and sepsis. In combined membrane‐adsorption systems, the patient's plasma is continuously separated from whole blood by means of a hollow fiber filter, and pathogenic factors are removed from the plasma by selective or specific adsorbents. While adsorbent particles with a size range of 300–800 µm are used in conventional systems, we are currently developing a system based on adsorbent microparticles (1–5 µm), the Microspheres‐Based Detoxification System (MDS). The characteristics of the matrix used for immobilization of specific ligands influence the performance of the resulting adsorbents. Desirable matrix characteristics are an open porous structure with an inner surface accessible for target molecules, mechanical stability, narrow particle size distribution, and ease of derivatization. In addition, biocompatibility is a critical issue, since the particles are in direct contact with the patient's plasma. Cellulose represents an ideal support matrix, as it combines all the above‐mentioned features, and cellulosic polymers are widely applied in medicine and generally regarded as biocompatible. Cellulose microparticles can be activated using e.g. sodium periodate and functionalized with Polymyxin B or anti‐tumor necrosis factor (TNF) antibodies to generate specific adsorbents for endotoxins or TNF. In summary, cellulose microparticles represent an excellent matrix as basis for adsorbent development in blood purification.

Integrated process for preparing porous, surface functionalized polyetherimide microparticles

“…A key challenge in this context is that the surfaces of absorbers prepared from hydrophobic materials are rapidly coated with proteins when being in contact with blood. Therefore, hydrophilic modifications are applied which typically require an additional processing step . One strategy to accelerate the development and translation of such multifunctional polymeric biomaterials is the establishment of integrated processes combining several single steps of the workflow resulting in a reduction of the processing time, and in this way the efficiency of development chains will be improved …”

Preparation and characterization of cellulose microspheres

“…This combined membraneadsorption system can be applied for the modulation of pathogenic mediator concentrations in sepsis and multiorgan failure. For this application, cellulose microspheres are functionalized by covalent binding of antibodies, antibody fragments or other bioactive molecules (Falkenhagen et al 2006;Weber et al 2010).…”

“…With these typical properties bead cellulose represents an excellent matrix as basis for developing adsorbents for extracorporeal blood purification. After activation and covalent immobilization of bioactive ligands, such as antibodies, cellulose microspheres represent efficient adsorbents for suspension-based extracorporeal blood purification systems (Ash et al 2006;Weber et al 2010).…”

Characterization and functionalization of cellulose microbeads for extracorporeal blood purification

“…Porous cellulose beads are widely used as separation media for chromatography and as micro-carriers in biotechnology, and have also found application as adsorbents in extracorporeal blood purification (Peška et al 1976;Kuga 1980;Boeden et al 1991;Wolf and Horsch 1991;Kaster et al 1993;De Oliveira and Glasser 1996;Wolf 1998;Volkert et al 2009;Weber et al 2010). In the latter field, combined membraneadsorption systems are established for the supportive therapy of various diseases, such as liver failure, autoimmune diseases, sepsis, and multi-organ failure Stegmayr 2005;Okafor et al 2010).…”