Stimuli-responsive and hemocompatible pseudozwitterionic interfaces.

We report a novel biomacromolecular formula for the design of hemocompatible gel interfaces of N-isopropylacrylamide (NIPAAm) and mixed-charge pairs of [2-(methacryloyloxy)ethyl]trimethylammonium (TMA) and 3-sulfopropyl methacrylate (SA) with overall electrical neutrality. The study stresses on how well-defined compositions of nonionic NIPAAm and pseudozwitterionic TMA/SA in the poly(NIPAAm-co-TMA/SA) hydrogels along with environmental conditions (temperature, ionic strength, and solution pH) affect swelling and adhesion of biofoulants on their surfaces. When challenged with plasma proteins, bacteria, recalcified platelets, or whole blood, stimuli-responsive hydrogels better resisted their adhesion as the content of mixed charges in the copolymer increased, to reach nonbiofouling for the gels made of 100% TMA/SA. The low hemolytic activity (0.5%) associated with a long plasma clotting time (10 min) suggests excellent hemocompatibility excellent hemocompatibility. Finally, hydrogels containing both NIPAAm and TMA/SA tend to exhibit preferential adhesion of leukocytes.

Hemocompatible control of sulfobetaine-grafted polypropylene fibrous membranes in human whole blood via plasma-induced surface zwitterionization.

In this work, the hemocompatibility of zwitterionic polypropylene (PP) fibrous membranes with varying grafting coverage of poly(sulfobetaine methacrylate) (PSBMA) via plasma-induced surface polymerization was studied. Charge neutrality of PSBMA-grafted layers on PP membrane surfaces was controlled by the low-pressure and atmospheric plasma treatment in this study. The effects of grafting composition, surface hydrophilicity, and hydration capability on blood compatibility of the membranes were determined. Protein adsorption onto the different PSBMA-grafted PP membranes from human fibrinogen solutions was measured by enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies. Blood platelet adhesion and plasma clotting time measurements from a recalcified platelet-rich plasma solution were used to determine if platelet activation depends on the charge bias of the grafted PSBMA layer. The charge bias of PSBMA layer deviated from the electrical balance of positively and negatively charged moieties can be well-controlled via atmospheric plasma-induced interfacial zwitterionization and was further tested with human whole blood. The optimized PSBMA surface graft layer in overall charge neutrality has a high hydration capability and keeps its original blood-inert property of antifouling, anticoagulant, and antithrmbogenic activities when it comes into contact with human blood. This work suggests that the hemocompatible nature of grafted PSBMA polymers by controlling grafting quality via atmospheric plasma treatment gives a great potential in the surface zwitterionization of hydrophobic membranes for use in human whole blood.

Surface charge-bias impact of amine-contained pseudozwitterionic biointerfaces on the human blood compatibility.

This work discusses the impact of the charge bias and the hydrophilicity on the human blood compatibility of pseudozwitterionic biomaterial gels. Four series of hydrogels were prepared, all containing negatively-charged 3-sulfopropyl methacrylate (SA), and either acrylamide, N-isopropylacrylamide, 2-dimethylaminoethyl methacrylate (DMAEMA) or [2-(methacryloyloxy)ethyl]trimethylammonium (TMA), to form SnAm, SnNm, SnDm or SnTm hydrogels, respectively. An XPS analysis proved that the polymerization was well controlled from the initial monomer ratios. All gels present high surface hydrophilicity, but varying bulk hydration, depending on the nature/content of the comonomer, and on the immersion medium. The most negative interfaces (pure SA, S7A3, S5A5) showed significant fibrinogen adsorption, ascribed to the interactions of the αC domains of the protein with the gels, then correlated to considerable platelet adhesion; but low leukocyte/erythrocyte attachments were measured. Positive gels (excess of DMAEMA or TMA) are not hemocompatible. They mediate protein adsorption and the adhesion of human blood cells, through electrostatic attractive interactions. The neutral interfaces (zeta potential between -10mV and +10mV) are blood-inert only if they present a high surface and bulk hydrophilicity. Overall, this study presents a map of the hemocompatible behavior of hydrogels as a function of their surface charge-bias, essential to the design of blood-contacting devices.

Zwitterionic fibrous polypropylene assembled with amphiphatic carboxybetaine copolymers for hemocompatible blood filtration.

UNLABELLED: The present study serves three main functions. First, it presents a novel random copolymer, made of octadecyl acrylate hydrophobic blocks and 2-(dimethylamino)ethyl methacrylate hydrophilic groups, and it zwitterionic form. Second, random copolymer and zwitterionic random copolymer, OmDn and Z-OmDn, are used to modify polypropylene membranes by evaporation coating. Our investigations unveil that this method leads to sufficiently stable self-assembling provided a minimum number of hydrophobic repeat units of 77, which also corresponds to a hydrophobic degree of 74%. Third, antifouling and hemocompatible properties of membranes are thoroughly investigated using all types of blood cells separately, as well as challenging membranes against whole blood in static and dynamic conditions. Membranes modified with zwitterionic copolymer containing 26% of zwitterionic groups are shown to be highly antifouling and hemocompatible, for a coating density as low as 0.2mg/cm(2). Their application in a specially designed blood filtration module enabled to almost totally inhibit blood cells interactions with membrane material, as well as to importantly reduce platelet activation in the permeate (2.5-fold reduction). STATEMENT OF SIGNIFICANCE: The design of new zwitterionic copolymer material is proposed and demonstrated in this study. It was showed that hydrophobicoctadecyl acrylate segments can be introduced in the zwitterioniccarboxybetaine polymer chain with a well-controlled random sequence. Stable, efficient, and effective surface zwitterionization of hydrophobic polypropylene are obtained via grafting onto approach by evaporation-induced self-assembling coating. In the perspective of potential application, hemocompatible blood filtration was demonstrated with the excellent results of non-activated platelets obtained. DESIGN: New zwitterionicmaterial, amphiphatic carboxybetaine copolymers. DEVELOPMENT: Evaporation-induced self-assembling grafting. APPLICATION: Hemocompatible blood filtration.