Surface modification of the polymers present in a polysulfone hollow fiber hemodialyser by covalent binding of heparin or endothelial cell surface heparan sulfate: Flow characteristics and platelet adhesion

Abstract

The present study addresses the problem of simultaneous surface modification of various polymers, i.e. polysulfone (PSU), polycarbonate (PC), and polyurethane (PU), which constitute the Ultraflux AV 600 S hollow fibre hemodialyser. An investigation was first made into six different chemical routes aimed at introducing carboxyl groups onto the surface of PSU, PC, and PU model polymers to which heparin (HE) or endothelial cell surface heparan sulfate (ESHS) was covalently bound via the reaction of residual amino groups and a coupling reagent. Carboxyl groups were introduced using three specific reactions based on their nucleophilic or electrophilic introduction into aromatic repeating units of the polymers and three non-specific carboxylation reactions, i.e. UV, heat or redoxactivation via nitrene or radical species. Concentrations of 1-20 nmol COOH groups per cm(-2) led to HE or ESHS surface concentrations corresponding to one or several layers. Two nonspecific carboxylation reactions followed by HE- or ESHS-coupling provided the lowest change in membrane pore structure according to cut off, clearance (urea, phosphate, maltose), ultrafiltration, and diafiltration assessments. In some cases the introduction of excess negatively-charged carboxyl groups and HE improved the flux properties of the modified membranes. The various methods were applied to the dialysis module. Platelet adhesion was not observed in the case of the ESHS-coating of PSU membrane at shear rates of 1050 s(-1), whereas HE and subendothelial matrix showed 56 and 100% coverage, respectively, under similar conditions. The coating of PSU or of other high-flux membranes by ESHS appears a promising method for improving membrane properties and to generate biocompatibility characteristics similar to those of natural blood vessels, i.e. inertness to platelet adhesion and no level effects for complement and intrinsic coagulation cascade activation. The ESHS coating may be used without anticoagulants.

Concepts for preparation of novel regioselective modified cellulose derivatives sulfated, aminated, carboxylated and acetylated for hemocompatible ultrathin coatings on biomaterials

“…[16] Mixed C2/C3 sulfated cellulose as well as only C3 sulfated cellulose showed the lowest platelet adhesion. More pronounced is the influence of 3 positions of sulfate groups in the HE of glucosamin moiety and the 2 position of iduronic acid.…”

“…Low concentrations or no 6-O-sulfate and low concentrations of N-sulfate but high concentrations of Nacetyl groups are necessary for the most important properties of surfaces of biomaterials the platelet inertness [15] or athrombogenicity. [16] Tab. 1.…”

Surface modification of polysulfone based hemodialysis membranes with layer by layer self assembly of polyethyleneimine/alginate-heparin: a simple polyelectrolyte blend approach for heparin immobilization

“…The most commonly used approach is to mimic endothelial cell layer by heparin immobilization. The beneficiary effect of heparin coatings on the membranes has been reported by many authors both in vitro [1][2][3][4][5][6][7][8][9] and in vivo [10][11][12][13][14][15]. For example, Cheung et al [1] observed that complement activation induced by hemodialysis can be modulated with heparin immobilized cellulose acetate membrane.…”

“…For example, Cheung et al [1] observed that complement activation induced by hemodialysis can be modulated with heparin immobilized cellulose acetate membrane. Baumann and Kokott [2] immobilized endothelial cell surface heparin sulfate (ESHS) on polysulfone (PSF), polycarbonate and polyurethane membranes and they found that the coating of these membranes by ESHS allows to generate surfaces resistant to platelet adhesion and have no effects on complement and intrinsic coagulation cascade activation. Yang and Lin [3,4] and Lin et al [5] covalently bonded chitosan/heparin conjugate onto the surface of PAN and PSF membranes and they reported improved biocompatibility of these membranes by evaluating coagulation time, plasma protein adsorption capacity and platelet adhesion [1][2][3][4][5].…”

“…Baumann and Kokott [2] immobilized endothelial cell surface heparin sulfate (ESHS) on polysulfone (PSF), polycarbonate and polyurethane membranes and they found that the coating of these membranes by ESHS allows to generate surfaces resistant to platelet adhesion and have no effects on complement and intrinsic coagulation cascade activation. Yang and Lin [3,4] and Lin et al [5] covalently bonded chitosan/heparin conjugate onto the surface of PAN and PSF membranes and they reported improved biocompatibility of these membranes by evaluating coagulation time, plasma protein adsorption capacity and platelet adhesion [1][2][3][4][5]. Zhu et al [6], Jiang et al [7] and Huang et al [8,9] also improved blood compatibilities of the poly(vinylidene fluoride), polyethylene (PE) and PSF membranes by covalent attachment of heparin [6][7][8][9].…”