Synthetically modified cellulose (SMC): a cellulosic hemodialysis membrane with minimized complement activation.

Abstract

More dialysis treatments have been performed with cellulose based membranes than with any other material. As unmodified cellulose membranes activate the complement system, much effort has been directed toward the development of noncomplement activating cellulose membranes. One successful approach was the substitution of -OH groups in the cellobiose units of the cellulose molecule with tertiary amino groups, which resulted in a membrane called Hemophan. Synthetically modified cellulose (SMC) is a new hemodialysis membrane made by specific chemical modification whereby aromatic benzyl groups are covalently introduced into the cellulosic structure by ether bonds, creating hydrophobic domains within the overall hydrophilic cellulose surface: basic research investigations have shown that a characteristic hydrophobic-hydrophilic balance of surfaces is a prerequisite for improved hemocompatibility. Several cellulose modifications with aliphatic and aromatic groups were performed to achieve a membrane with the desired hemocompatibility profile; SMC, having hydrophobic benzyl groups, causes minimal activation of blood complement, coagulation, and cell activation systems. In vitro experiments with blood showed that C5a generation for SMC was reduced by 94% relative to Cuprophan (compared with 96% for polysulphone, a synthetic hemodialysis membrane). Activation of coagulation (formation of the thrombin-antithrombin III complex [TAT]) in a clinical study showed that SMC caused 16 ng/ml TAT generation compared with 36 ng/ml for polysulphone. SMC, a low-flux cellulosic dialysis membrane, thus combines the typically high diffusive performance characteristics of cellulosic membranes with excellent hemocompatibility, matching synthetic dialysis membranes.