Recent Developments and Current Challenges of Heparin-Grafted Hemodialysis Membranes

Abstract

Hemodialysis (HD) is a life-sustaining extracorporeal blood purifying treatment for end-stage renal disease (ESRD) patients. However, this membrane-based therapy is associated with acute side effects, life-threatening chronic conditions, and unacceptably high morbidity and mortality rates. Numerous surface coatings have been developed to improve the blood compatibility of biomaterials. Heparin is a widely used anticoagulant substance that increases the clotting time and increases the membrane hemocompatibility in terms of platelet adhesion and protein adsorption and anti-clotting activity. However, using heparin is challenging due to its severe or life-threatening side effects such as heparin-induced thrombocytopenia (HIT), in addition to heparin induced thrombocytopenia and thrombosis (HITT). In addition, heparin is strongly electronegative and exhibits a binding affinity for the positive active sites of human serum proteins, which is an additional challenge. Consequently, covalently immobilized heparin would create a more charged surface to induce more blood–membrane interactions, and consequently more adsorbed human serum proteins and biochemical pathway activations, which can negatively affect dialysis patients. Therefore, the current critical review has thoroughly focused on different heparin HD membrane systems, the challenges of heparin-coated dialysis membranes, and the factors affecting its hemocompatibility, in addition to the methods that can be used to enhance its hemocompatibility. Furthermore, this review summarizes the advantages and disadvantages of heparin-grafted methods. Furthermore, the influence of the heparin-immobilization method on the hemocompatibility and performance of the HD membrane was comprehensively analyzed. Finally, we conclude with the future perspectives for the strategies toward the heparinization and heparin-like/mimicking modification of membrane surfaces.