Biocompatibility and functional performance of a polyethylene glycol acid-grafted cellulosic membrane for hemodialysis

In order to improve the biochemical reactivity of the cellulose polymer, wh ich is mainly attributed to the presence of surface hydroxyl groups, deriva tized cellulosic membranes have been engineered replacing or masking some o r all of the hydroxyl groups in the manufacturing process of the membrane. The present study was set up to analyze both biocompatibility and functiona l performance of two different derivatized cellulosic membranes (cellulose diacetate; polyethylene glycol, PEG, acid-grafted cellulose) as compared to a synthetic membrane (polymethylmethacrylate, PMMA). Cellulose diacetate i s prepared by substituting hydroxyl groups with acetyl groups; PEG cellulos e is obtained by grafting PEG chains onto the cellulosic polymer with a sma ller amount of substitution than cellulose diacetate. While the three dialyzers provided similar urea and creatinine removal, the dialyzer containing cellulose diacetate showed a reduced ability to remove R2-microglobulin compared to that containing PEG cellulose or PMMA. A tran sient reduction in leukocyte count was observed for both derivatized cellul osic membranes. The neutrophil and monocyte counts throughout the entire di alysis session showed a closer parallelism with the cellular expression of the adhesive receptor CD15s (sialyl-Lewis x molecole) than with CD11b/CD18 expression. Platelet activation, as indicated by the percentage of cells ex pressing the activation markers CD62P (P-selectin) and CD63 (gp53), occurre d with all membranes at 15 min of dialysis and also with PMMA at 30 min. An increased formation of platelet-neutrophil and platelet-monocyte coaggrega tes was found at 15 and 30 min during dialysis with cellulose diacetate and PMMA but not with PEG cellulose. Generally in concomitance with the increa se in platelet-neutrophil coaggregates, an increased hydrogen peroxide prod uction by neutrophils occurred. Our results indicate that derivatizing cell ulose may represent a useful approach to improve the biocompatibility of th e cellulose polymer, though some homeostatic reactions remain activated Our results also indicate that there may be a great variability in the bioc ompatibility profile of derivatized cellulosic membranes which most likely stem from the different type of structural modification rather than from th e degree of hydroxyl group replacement.