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| 16. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Blood protein-polymer adsorption fingerprinting: Implications for understanding hemoocompatibility and for biomaterial design.
- 2011
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Ingår i: Journal of Biomedical Materials Research. Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 97A:1, s. 74-84
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to create polymeric materials with known properties to study the preconditions for complement activation. Initially, 22 polymers were screened for complement activating capacity. Based on these results, six polymers (P1-P6) were characterized regarding physico-chemical parameters, for example, composition, surface area, pore size, and protein adsorption from human EDTA-plasma. P2, P4, and reference particles of polystyrene and polyvinyl chloride, were hydrophobic, bound low levels of protein and were poor complement activators. Their accessible surface was limited to protein adsorption in that they had pore diameters smaller than most plasma proteins. P1 and P3 were negatively charged and adsorbed IgG and C1q. A 10-fold difference in complement activation was attributed to the fact that P3 but not P1 bound high amounts of C1-inhibitor. The hydrophobic P5 and P6 were low complement activators. They selectively bound apolipoproteins Al and AIV (and vitronectin), which probably limited the binding of complement activators to the surface. We demonstrate the usefulness of the modus operandi to use a high-throughput procedure to synthesize a great number of novel substances, assay their physico-chemical properties with the aim to study the relationship between the initial protein coat on a surface and subsequent biological events. Data obtained from the six polymers characterized here, suggest that a complement-resistant surface should be hydrophobic, uncharged, and have a small available surface, accomplished by nanostructured topography. Additional attenuation of complement can be achieved by selective enrichment of inert proteins and inhibitors.
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| 17. |
- Rosengren-Holmberg, Jenny P., et al.
(författare)
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Heparin molecularly imprinted surfaces for the attenuation of complement activation in blood
- 2015
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Ingår i: Biomaterials Science. - : Royal Society of Chemistry (RSC). - 2047-4830 .- 2047-4849. ; 3:8, s. 1208-1217
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Tidskriftsartikel (refereegranskat)abstract
- Heparin-imprinted synthetic polymer surfaces with the ability to attenuate activation of both the complement and the coagulation system in whole blood were successfully produced. Imprinting was achieved using a template coated with heparin, a highly sulfated glycosaminoglycan known for its anticoagulant properties. The N,N'-diacryloylpiperazine-methacrylic acid copolymers were characterized using goniometry, AFM and XPS. The influence of the molecular imprinting process on morphology and template rebinding was demonstrated by radioligand binding assays. Surface hemocompatibility was evaluated using human whole blood without anticoagulants followed by measurement of complement activation markers C3a and sC5b-9 and platelet consumption as a surrogate coagulation activation marker. The observed low thrombogenicity of this copolymer combined with the attenuation of complement activation induced by the molecular imprint offer potential for the development of self-regulating surfaces with important potential clinical applications. We propose a mechanism for the observed phenomena based upon the recruitment of endogenous sulfated glycosaminoglycans with heparin-like activities.
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- Rosengren-Holmberg, Jenny P., et al.
(författare)
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Synthesis and ligand recognition of paracetamol selective polymers: semi-covalent versus non-covalent molecular imprinting.
- 2009
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Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 7, s. 3148-3155
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Tidskriftsartikel (refereegranskat)abstract
- Three molecular imprinting strategies, each based upon a series of ethylene glycol dimethacrylate (EGDMA) cross-linked co-polymers, have been used to produce materials selective for the commonly used analgesic and antipyretic agent paracetamol (p-acetaminophen or 4-acetamidophenol) (1). The polymers were synthesised using either a semi-covalent imprinting strategy based upon 4-acetamidophenyl-(4-vinylphenyl) carbonate (4) or a non-covalent strategy based on methacrylic acid (MAA) as the functional monomer, or by employing a combination of these strategies. Radioligand binding studies demonstrated low template affinity in polymers offering only a single electrostatic interaction point for recognition via the phenolic residue in the template, whereas binding was substantially increased upon the introduction of a second binding mode, namely interaction at the acetamide moiety. HPLC analyses revealed no imprinting effect in the purely semi-covalent system, and only a minor effect in the purely non-covalent systems. However, a pronounced imprinting effect was demonstrated for polymers prepared by a combination of semi-covalent and non-covalent imprinting. This study illustrates a limitation of both the non-covalent and the semi-covalent strategies when it comes to achieving imprinted selectivity for small and poorly functionalised templates such as paracetamol. Parallels with conclusions from studies with antibodies are discussed.
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