Chemically modified poly(2-hydroxyethyl methacrylate) cryogel for the adsorption of heparin

Various clinical procedures, such as cardiovascular surgery or extracorporeal blood purification, involve systemic anticoagulation using heparin. High concentrations of circulating heparin require neutralization due to possible serious bleeding complications. The intravenous administration of the heparin antagonist protamine sulfate is routinely clinically performed, but is frequently associated with adverse reactions. Therefore, there is a need for a valid and safe alternative to achieve extracorporeal heparin removal from blood or plasma, such as a filter, a matrix, or an adsorbent. Here, we describe the development of a macroporous poly(2-hydroxyethyl methacrylate)-based monolithic cryogel functionalized with l-lysine (pHEMA-lys) and the characterization of its selective heparin adsorption. The maximum binding capacity was quantified in vitro using aqueous and serum solutions under static and dynamic conditions, and fresh human plasma under static conditions. The pHEMA-lys bound 40,500 IU and 32,500 IU heparin/g cryogel at the equilibrium in aqueous solution and 50% serum, respectively. In human plasma spiked with 100 IU/mL of heparin, the binding was still highly efficient (4330 IU/g cryogel after 30 min, i.e., 87% of the initial concentration). The cryogels showed good blood compatibility, as indicated by negligible adsorption of albumin, antithrombin III, and total protein, and may thus be suitable for extracorporeal heparin removal.