Michael Diamantoglou

Artificial Dialysis Membranes: From Concept to Large Scale Production

The development of hemodialysis from an experimental concept to a routine medical therapy is closely related to research, manufacturing and availability of dialysis membranes. Collodion, a cellulose-trinitrate derivative, was the first polymer to be used as an artificial membrane and played a central role in further investigations and applications. Basic studies on the mechanism of solute transport through membranes, like diffusion, were done by A. Fick and T. Graham using collodion as a membrane material. In vivo dialysis in animals and humans was performed with collodion by J. Abel in the USA and G. Haas in Germany. Cellophane and Cuprophan membranes replaced collodion later, because of their better performance and mechanical stability. However, due to its alleged lack of hemocompatibility, membranes made from unmodified cellulose lost their market share. They have been replaced by modified cellulosic and synthetic dialysis membranes which show a better hemocompatibility than unmodified cellulose membranes. Most of the new membrane materials are also available in high-flux modifications and for this reason suitable as well for more effective therapy modes, such as hemodiafiltration and hemofiltration. The success of hemodialysis as a routine therapy is also the success of membrane development, because both, a reproducible membrane production and an unlimited availability of dialysis membranes have increased the number of dialyzed patients to about 1 million patients worldwide in 1999.

Cellulose-Ester as Membrane Materials for Hemodialysis

The majority of dialysis membranes are fabricated from regenerated unmodified cellulose. This standard type of cellulosic membrane is frequently under attack because of its alleged lack of biocompatibility. Recent developments, however, have proven that a chemical modification of the reactive surface groups of regenerated cellulose, the hydroxylgroups, limits the complement-activating potential of these materials and thus improves its blood-compatibility. We extended the idea of modifying cellulose for improved blood-compatibility to a series of different cellulose esters. Special focus was directed towards the question whether a variation of the type of substituent and degree of substitution could influence the blood-compatibility pattern of these materials: the analysis of blood-compatibility profiles showed a direct dependency on the type of substituent and the degree of substitution (DS). As an example, it was found that the DS, necessary for a complete reduction of complement activation, decreases with increasing chain lengths of aliphatic substituents. Optimal degrees of substitution are characteristic of the type of substituents and enable us to tailor materials specifically for optimized blood compatibility.