RESUMEN
Polymers are widely used for a large range of medical devices used as biomaterials on a temporary, intermittent, and long-term basis. It is now well accepted that the initial rapid adsorption of proteins to polymeric surfaces affects the performance of these biomaterials. However, protein adsorption to a polymer surface can be modulated by an appropriate design of the interface. Extensive study has shown that these interactions can be minimized by coating with a highly hydrated layer (hydrogel), by grafting on the surface different biomolecules, or by creating domains with chemical functions (charges, hydrophilic groups). Our laboratory has investigated the latter approach over the past 2 decades, in particular the synthesis and the biological activities of polymers to improve the biocompatibility of blood-contacting devices. These soluble and insoluble polymers were obtained by chemical substitution of macromolecular chains with suitable groups able to develop specific interactions with biological components. Applied to compatibility with the blood and the immune systems, this concept has been extended to interactions of polymeric biomaterials with eukaryotic and prokaryotic cells. The design of new biomaterials with low bacterial attachment is thus under intensive study. After a brief overview of current trends in the surface modifications of biocompatible materials, we will describe how biospecific polymers can be obtained and review our recent results on the inhibition of bacterial adhesion using one type of functionalized polymer obtained by random substitution. This strategy, applied to existing or new materials, seems promising for the limitation of biomaterial-associated infections.
Asunto(s)
Adhesión Bacteriana , Materiales Biocompatibles/farmacocinética , Polímeros/farmacocinética , Adsorción , Materiales Biocompatibles/efectos adversos , Materiales Biocompatibles/química , Dextranos/farmacocinética , Humanos , Polímeros/química , Propiedades de SuperficieRESUMEN
The contact of blood with some biomaterials results in complement activation, primarily by the alternative pathway (AP). Insoluble polystyrene derivatives bearing isolated sulphonate groups (PSSO3) deplete complement, whereas identical surfaces substituted with both sulphonate and hydroxymethyl groups (PSCH2OH-SO3) are non-activators. Polystyrene sulphonate derivatives possess high adsorptive properties, particularly for serine proteases of the coagulation cascade. Thus, we studied the interactions between polystyrene derivatives and factor D, an enzyme essential for AP activation. C3 was activated when normal human serum (NHS) was incubated with PSSO3, whereas PSCH2OH-SO3 did not induce any specific C3 activation. Both polymers adsorbed factor D from serum, as shown by the loss of haemolytic factor D from NHS incubated with the polymers and by the specific adsorption of radiolabelled factor D. When bound to the polymers, factor D was not functional. The disappearance of factor D was in contradiction to the observed complement activation induced by PSSO3. When other AP components were studied, it was evident that PSSO3 adsorbed factor H even more rapidly and efficiently than factor D. Thus, the net effect was an immediate deregulation of the AP resulting in C3 activation, followed by inhibition of the AP when factor D was finally depleted. Pre-exposure of PSSO3 to NHS prevented any complement activation because the polymer was saturated with factor H, but still adsorbed factor D. Such properties could be beneficial during haemodialysis with membranes for uremic patients who have increased levels of factor D in their serum.
Asunto(s)
Materiales Biocompatibles/química , Complemento C3c/metabolismo , Factor D del Complemento/química , Vía Alternativa del Complemento , Poliestirenos/química , Electroforesis en Gel de Poliacrilamida , Humanos , Poliestirenos/farmacologíaRESUMEN
Reducing the complement-activating capacity of a polymer surface is important in improving its blood compatibility. Polystyrene surfaces bearing hydroxymethyl (CH2OH) groups activate the alternative pathway of complement. This activation depends strongly on the density of the groups. Polystyrene surfaces bearing sulphonate (SO3-) groups adsorb proteins, resulting in an apparent activation. Polystyrene surfaces bearing both types of groups in close proportions are not activators in human serum, due to the adsorption of a protein of the alternative pathway, which has a protecting effect, not found when a polymer surface bearing hydroxyl groups is mixed in serum with another polymer surface bearing SO3- groups. In the presence of purified proteins of alternative pathway, C3 convertase activity can be created on each of these surfaces by deposition of C3b, but their susceptibility to inactivation by regulatory proteins H and I depends on the types of chemical groups present on the surface and whether the surfaces were passivated or not before C3b deposition.
Asunto(s)
Bencenosulfonatos/farmacología , Materiales Biocompatibles , Activación de Complemento , Poliestirenos , Adsorción , Materiales Biocompatibles/química , Proteínas Sanguíneas/metabolismo , Convertasas de Complemento C3-C5/metabolismo , Complemento C3c/inmunología , Complemento C3c/metabolismo , Humanos , Técnicas In Vitro , Poliestirenos/químicaRESUMEN
The interactions between blood and polymer surfaces used in extracorporeal circulations result in variable activations of the immune system of complement. Measuring concentrations of C3a or C5a in supernatant blood or serum after contact with the surface has been the most usual way of assessing this activation. Most polymer surfaces bearing various chemical groups were found to adsorb C3a and sometimes C5a. After taking into account adsorption, a good correlation was found between total C3a generated and CH50 units consumed by most of the polymer samples tested. Measuring only C3a remaining in the fluid phase should not be considered sufficient to conclude that a material surface is not an activator of complement.
Asunto(s)
Activación de Complemento/efectos de los fármacos , Fragmentos de Péptidos/farmacocinética , Polímeros/farmacocinética , Adsorción , Complemento C3a/análogos & derivados , Complemento C3a/biosíntesis , Complemento C3a/metabolismo , Dextranos/química , Dextranos/farmacología , Humanos , Fragmentos de Péptidos/sangre , Polímeros/química , Poliestirenos/química , Poliestirenos/farmacología , Propiedades de SuperficieRESUMEN
The interactions between blood and insoluble polysaccharidic surfaces result in activation of the immune system of complement. When substituted with carboxymethyl groups, Sephadex loses its capacity to activate complement, whereas Sephadex sulphate has been described as an activator. In order to elucidate the molecular mechanisms of complement activation and inhibition, a simpler polymer model has been chosen: it consists of an insoluble polystyrene backbone on which either isolated hydroxymethyl or sulphonate groups or both are present. The surfaces bearing the isolated groups consume complement but the mechanisms involved are quite different. In contrast, a surface bearing equal proportions of both types of groups is a non-activator. Such model surfaces can be very useful for designing artificial surfaces able to control in situ complement activation.