Cellulose carbamates and derivatives as hemocompatible membrane materials for hemodialysis

Dialysis membranes made from regenerated cellulose are under dispute because of their alleged lack of hemocompatibility. The introduction of membranes from synthetically modified cellulose, like cellulose acetate or Hemophan, has proven, however, that hemocompatible membranes can be fabricated from cellulose by means of chemical surface modifications. In addition to membranes made from modified cellulose like ethers or esters, which were investigated in earlier experiments, we looked for further cellulose modifications to be assessed for their hemocompatibility. For this purpose, we synthesized a series of cellulose carbamate derivatives to profit from the excellent hemocompatibility pattern of the urethane family. In vitro investigations on membranes made from these cellulose modifications proved a direct relationship between the degree of modification and hemocompatibility. This was proven for the following 3 representative hemocompatibility parameters: complement C5a generation, thrombin-antithrombin (TAT) III formation, and platelet count (PC). As already shown for modifications made from cellulose esters, a direct dependency between improved hemocompatibility and the degree of substitution (DS) in the cellulose molecule could be found. In our experiments, a degree of substitution below a value of 0.1 led to a nearly complete suppression of complement activation for all cellulose carbamates under investigation. In contrast to data on cellulose esters, we observed that molecular weight or molecular conformation of chemical substituents exerted only a minor effect on the hemocompatibility pattern. In addition, data on cellulose carbamate esters (e.g., cellulose succinate-phenyl-carbamate) show that a simultaneous but balanced substitution with hydrophilic and hydrophobic groups at the surface of the cellulose polymer is a further prerequisite for optimal hemocompatibility. It seems that the carbamate configuration per se has a positive effect on the hemocompatibility pattern of synthetically modified cellulose membranes.