Structure and biocompatibility of poly(vinyl alcohol)-based and agarose-based monolithic composites with embedded divinylbenzene-styrene polymeric particles.

Macroporous monolithic composites with embedded divinylbenzene-styrene (DVB-ST) polymeric particles were prepared by cryogelation techniques using poly(vinyl alcohol) or agarose solutions. Scanning electron microscopy images showed multiple interconnected pores with an average diameter in the range of 4 to 180 µm and quite homogeneous distribution of DVB-ST particles in the composites. Biocompatibility of the composites was assessed by estimation of the C5a fragment of complement in the blood serum and concentration of fibrinogen in the blood plasma which contacted the composites. A time-dependent generation of C5a fragment indicated weak activation of the complement system. At the same time, the difference in fibrinogen concentration, one of the most important proteins in the coagulation system of the blood, between the pristine blood plasma and the plasma, circulated through the monolithic columns, was insignificant.

Composite cryogel with immobilized concanavalin A for affinity chromatography of glycoproteins.

Composite cryogels containing porous adsorbent particles were prepared under cryogelation conditions. The composites with immobilized concanavalin A (Con A) were used for capturing glycoproteins. Adsorbent particles were introduced into the structure in order to improve the capacity and to facilitate the handling of the particles. The monolithic composite cryogels were produced from suspensions of polyvinyl alcohol particles and porous adsorbent particles and cross-linked under acidic conditions at sub-zero temperature. The cryogels were epoxy activated and Con A was immobilized as an affinity ligand. Binding and elution of horseradish peroxidase (HRP) was studied in batch experiment and in a chromatographic setup. Increasing adsorbent concentration in composite cryogels will increase ligand density, which therefore enhances the amount of bound HRP from 0.98 till 2.9 (milligram enzyme per milliliter of gel) in the chromatographic system. The material was evaluated in 10 cycles for binding and elution of HRP.

Effect of anticoagulation with citrate versus heparin on the adsorption of coagulation factors to blood purification resins with different charge.

In liver failure, hydrophobic toxins accumulate in the blood circulation. To support hepatic function, extracorporeal blood purification systems have been developed, in which both cationic and neutral adsorbents are used to remove albumin-bound metabolites from blood. An issue of these systems is the additional removal of coagulation factors containing negatively charged γ-carboxyglutamate (Gla) domains, which, in physiological conditions, are shielded by calcium ions. We hypothesized that complexation of calcium ions by citrate leads to exposure of negative Gla domains, resulting in their binding to the positively charged adsorbents. The data presented here confirm that the binding of coagulation factors containing Gla domains to positively charged polymers is enhanced in the presence of citrate as compared to heparin. This effect increased with increasing charge density of the polymer and has important implications for the clinical application of positively charged polymers.

High efficiency removal of dissolved As(III) using iron nanoparticle-embedded macroporous polymer composites.

Novel nanocomposite materials where iron nanoparticles are embedded into the walls of a macroporous polymer were produced and their efficiency for the removal of As(III) from aqueous media was studied. Nanocomposite gels containing α-Fe(2)O(3) and Fe(3)O(4) nanoparticles were prepared by cryopolymerisation resulting in a monolithic structure with large interconnected pores up to 100 µm in diameter and possessing a high permeability (ca. 3 × 10(-3) ms(-1)). The nanocomposite devices showed excellent capability for the removal of trace concentrations of As(III) from solution, with a total capacity of up to 3mg As/g of nanoparticles. The leaching of iron was minimal and the device could operate in a pH range 3-9 without diminishing removal efficiency. The effect of competing ions such as SO(4)(2-) and PO(4)(3-) was negligible. The macroporous composites can be easily configured into a variety of shapes and structures and the polymer matrix can be selected from a variety of monomers, offering high potential as flexible metal cation remediation devices.

Neutral styrene divinylbenzene copolymers for adsorption of toxins in liver failure.

In artificial extracorporeal liver support systems, albumin-bound toxins such as bilirubin, bile acids, or aromatic amino acids are removed by adsorption to polymer beads. To overcome the potential weaknesses of anion exchange polymers currently used in liver support, namely, binding of heparin and activation of coagulation, we prepared two series of neutral polystyrene divinylbenzene resins with average pore sizes of 5-6 and 8-9 nm, respectively. In in vitro experiments using human plasma spiked with bilirubin, cholic acid, tryptophan, and phenol, we found that only pores larger than 5-6 nm were accessible to strongly albumin-bound substances, such as bilirubin. On the other hand, less strongly albumin-bound substances, such as bile acids, were efficiently bound by polymers of the small pore size range due to a higher accessible surface area. None of the neutral resins bound significant amounts of heparin. To assess the influence of the polymers on activation of coagulation, generation of thrombin-antithrombin complexes (TAT) was measured at different citrate concentrations. While none of the neutral polymers induced TAT generation, TAT levels were significantly elevated after incubation of plasma with an anion exchange polymer that is in clinical use for extracorporeal liver support. Binding characteristics of the neutral resins for the natural anticoagulants protein C and antithrombin showed remarkable differences, with weak binding of antithrombin but strong removal of protein C, not only for the anion exchanger, but also for neutral polymers of the large pore size range. In conclusion, neutral polystyrene divinylbenzene polymers with a pore size larger than 5-6 nm are efficient adsorbents for albumin-bound toxins that do not induce generation of thrombin-antithrombin complexes.