Regenerated Cellulose‐Based Hemodialyzers with Immobilized Proteins as Potential Devices for Extracorporeal Immunoadsorption Procedures: An Assessment of Protein Coupling Capacity and In Vitro Dialysis Performances

Abstract

The development of immunoadsorbents usable with whole blood should offer the potential for making significant improvements in extracorporeal immunoadsorption procedures. In contrast to traditional chromatographic media, these hemocompatible matrices could be used without requiring the previous step of the separation of blood cells and plasma. Conventional hemodialyzers seem to be particularly appropriate for such a purpose. This paper describes a feasibility study of the preparation of immunoaffinity supports, from regenerated cellulose (Cuprophan)-based dialyzers by cyanogen bromide activation and coupling of bovine serum albumin or human immunoglobin G, used as models for immunochemical ligands. Several parameters of the activation and coupling steps were studied in order to define the optimum preparation conditions. In addition, the preservation of the transport properties (clearance and ultrafiltration) of the modified hemodialyzers was evaluated in vitro to ensure that the device potentially could be used in future human therapeutic applications with no risk of massive removal of solutes and fluid from the blood. Results indicate that 150-300 mg of immunoglobulins can be immobilized per square meter of Cuprophan. Modified hemodialyzers show a slight decrease of their clearance values and a slight increase of their ultrafiltration coefficients, and thus they can be proposed as reliable carrier material for extracorporeal cleansing systems.

Hemocompatibility and anaphylatoxin formation of protein-immobilizing polyacrylonitrile hemodialysis membrane

“…These values were respectively about 1.43 and 1.17 times of the untreated PAN membrane. In the literature, Laurent et al [2] reported that the Cuprophan hollow fiber coupled with bovine serum albumin (BSA) showed a slight increase in the ultrafiltration coefficient. Fig.…”

“…Many studies have aimed to improve hemocompatibility of biomaterials by surface modification [1][2][3][4][5][6][7]. The most widely used blood anticoagulant, heparin, can catalytically increase the rate that antithrombin III (ATIII) inhibits thrombin and some other coagulation proteases [8][9][10].…”

Limitations of Membrane Structure and Dialyzer Design on Large Solute Removal in Dialysis

“…Therefore, the development of membrane materials with a greater affinity for adsorption of beta-2-microglobulin could theoretically result in higher removal rates than could be achieved by convection and diffusion alone. As a logical extension, it has been proposed to immobilize proteins on the surface of dialysis membranes to act as immunoadsorptive devices for beta-2-microglobulin removal [12]. In both of these cases, the potential for beta-2-microglobulin removal by adsorption is limited by the surface area available for adsorption.…”

In Vitro Removal of Beta‐2‐Microglobulin From Uremic Blood With an Immunoadsorption Wall

“…Also, the application of immunoadsorption principles to the treatment of DRA has attracted many research interests during the past decades, and a variety of techniques and ingenuity have been combined with the inherent unique advantages of immunoadsorption to create useful, promising materials and modalities for the removal of β‐2M. For example, remarkable advances include production of monoclonal antibodies specific to β‐2M (18), regenerated cellulose‐based hemodialyzers with immobilized proteins (19), and an immunoaffinity‐based extracorporeal vortex flow plasmapheretic reactor (20). These achievements suggest the future potentials of reducing abnormally high levels of β‐2M in uremic blood by immunoadsorption.…”