Reducing the complement-activating capacity of a polymer surface is important in improving its bl... more 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 surfa...
The contact of blood with some biomaterials results in complement activation, primarily by the al... more 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 wa...
between blood and polymer surfaces used in extracorporeal circulations result in variable activat... more between blood and polymer surfaces used in extracorporeal circulations result in variable activations of the immune system of complement.
Journal of Biomaterials Science, Polymer Edition, 1991
The interactions between blood and insoluble polysaccharidic surfaces result in activation of the... more 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.
Biomaterials-centered infections are serious complications associated with the use of implants. T... more Biomaterials-centered infections are serious complications associated with the use of implants. The infection risk of biomaterials varies between different materials and is determined by the chemical composition of materials, the host proteins and the type of bacteria. In this study we measured the initial adhesion of Sfaphy/ococcus aureus onto polystyrene derivatives containing carboxylate and sulfonate groups. Five polymers were synthesized and characterized. We studied the role of the host protein fibronectin in promoting adhesion of Staphylococcus aureus. Fibronectin adsorption was comparable on all the tested polymers (pKd=7.2*0.2) whereas bacterial adhesion was dependent on surfaces chemical compositions. Polymers substituted with sulfonate groups showed the most important inhibition of initial bacterial adhesion. 0 2002 Editions scientifiques et medicales Elsevier SAS bacterial adhesion I biomaterials / biomimetic polymers / fibronectin R&urn6 -Modulation de I'adhkrence de Sfaphylococcus aureus par des copolym&res biofonctionnels d&iv& du polystyr&ne. L'adhkrence des bact&ies 2 la surface des biomakkiaux implantables aboutit dans la plupart des cas B la colonisation, &ape prkkdant /'infection en pathologic humaine. Le risque d'infection dgpend de la composition chimique des biomatkriaux, des protkines adsorb&es g la surface de ces mat.&iaux et du type de micro-organisme. Dans cette Etude, nous avons Btudih et quantifib I'adhkrence de Staphylococcus aureus, un des principaux responsables de /'infection sur corps &ranger, sur des polymkres d&iv& du polystyrkne porteurs de groupes carboxylate et sulfonate. Cinq polym&es de compositions diffgrentes ont Bt6 synth@tis& et caract&is6s Le r&e de la fibronecfine en tant que prot&ne mkdiatrice de l'adhbrence bactkrienne a &S &al&. Les r&u/fats obtenus montrent que /'adsorption de la fibronectine radiomarquee est identique sur /es cinq polym&res (pKd = 7.2 k 0.2) alors que l'adhkrence de Staphylococcus aureus sur /es surfaces prkadsorbkes de fibronectine dkpend de la composition chimique du polymkre. La pksence des groupements sulfonate permet d'obtenir I'effet inhibiteur de I'adhkrence bactkienne le plus important. 0 2002 Editions scientifiques et medicales Elsevier SAS adherence bacterienne / biomateriaox / fibronectine I polymeres biomimetiques * Correspondence and reprints.
The contact of blood with some biomaterials results in complement activation, primarily by the al... more The contact of blood with some biomaterials results in complement activation, primarily by the alternative pathway (AP). Insoluble polystyrene derivatives bearing isolated sulphonate groups (PSSO,) deplete complement, whereas identical surfaces substituted with both sulphonate and hydroxymethyl groups (PSCH,OH-SO,) 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 PSSO,, whereas PSCH20H-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 PSSOs. When other AP components were studied, it was evident that PSSOJ 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. Preexposure of PSSO, 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. Metabolism of complement factor D in renal failure, Kidney Int. 1988, 34, 529-536 Pascual, M., Paccaud, J.P., Macon, K., Volanakis, J.E. and Schifferli, J.A., Complement activation by the alternative pathway is modified in renal failure: the role of factor D,
between blood and polymer surfaces used in extracorporeal circulations result in variable activat... more between blood and polymer surfaces used in extracorporeal circulations result in variable activations of the immune system of complement.
Polymers are widely used for a large range of medical devices used as biomaterials on a temporary... more 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.
Reducing the complement-activating capacity of a polymer surface is important in improving its bl... more 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 surfa...
The contact of blood with some biomaterials results in complement activation, primarily by the al... more 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 wa...
between blood and polymer surfaces used in extracorporeal circulations result in variable activat... more between blood and polymer surfaces used in extracorporeal circulations result in variable activations of the immune system of complement.
Journal of Biomaterials Science, Polymer Edition, 1991
The interactions between blood and insoluble polysaccharidic surfaces result in activation of the... more 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.
Biomaterials-centered infections are serious complications associated with the use of implants. T... more Biomaterials-centered infections are serious complications associated with the use of implants. The infection risk of biomaterials varies between different materials and is determined by the chemical composition of materials, the host proteins and the type of bacteria. In this study we measured the initial adhesion of Sfaphy/ococcus aureus onto polystyrene derivatives containing carboxylate and sulfonate groups. Five polymers were synthesized and characterized. We studied the role of the host protein fibronectin in promoting adhesion of Staphylococcus aureus. Fibronectin adsorption was comparable on all the tested polymers (pKd=7.2*0.2) whereas bacterial adhesion was dependent on surfaces chemical compositions. Polymers substituted with sulfonate groups showed the most important inhibition of initial bacterial adhesion. 0 2002 Editions scientifiques et medicales Elsevier SAS bacterial adhesion I biomaterials / biomimetic polymers / fibronectin R&urn6 -Modulation de I'adhkrence de Sfaphylococcus aureus par des copolym&res biofonctionnels d&iv& du polystyr&ne. L'adhkrence des bact&ies 2 la surface des biomakkiaux implantables aboutit dans la plupart des cas B la colonisation, &ape prkkdant /'infection en pathologic humaine. Le risque d'infection dgpend de la composition chimique des biomatkriaux, des protkines adsorb&es g la surface de ces mat.&iaux et du type de micro-organisme. Dans cette Etude, nous avons Btudih et quantifib I'adhkrence de Staphylococcus aureus, un des principaux responsables de /'infection sur corps &ranger, sur des polymkres d&iv& du polystyrkne porteurs de groupes carboxylate et sulfonate. Cinq polym&es de compositions diffgrentes ont Bt6 synth@tis& et caract&is6s Le r&e de la fibronecfine en tant que prot&ne mkdiatrice de l'adhbrence bactkrienne a &S &al&. Les r&u/fats obtenus montrent que /'adsorption de la fibronectine radiomarquee est identique sur /es cinq polym&res (pKd = 7.2 k 0.2) alors que l'adhkrence de Staphylococcus aureus sur /es surfaces prkadsorbkes de fibronectine dkpend de la composition chimique du polymkre. La pksence des groupements sulfonate permet d'obtenir I'effet inhibiteur de I'adhkrence bactkienne le plus important. 0 2002 Editions scientifiques et medicales Elsevier SAS adherence bacterienne / biomateriaox / fibronectine I polymeres biomimetiques * Correspondence and reprints.
The contact of blood with some biomaterials results in complement activation, primarily by the al... more The contact of blood with some biomaterials results in complement activation, primarily by the alternative pathway (AP). Insoluble polystyrene derivatives bearing isolated sulphonate groups (PSSO,) deplete complement, whereas identical surfaces substituted with both sulphonate and hydroxymethyl groups (PSCH,OH-SO,) 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 PSSO,, whereas PSCH20H-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 PSSOs. When other AP components were studied, it was evident that PSSOJ 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. Preexposure of PSSO, 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. Metabolism of complement factor D in renal failure, Kidney Int. 1988, 34, 529-536 Pascual, M., Paccaud, J.P., Macon, K., Volanakis, J.E. and Schifferli, J.A., Complement activation by the alternative pathway is modified in renal failure: the role of factor D,
between blood and polymer surfaces used in extracorporeal circulations result in variable activat... more between blood and polymer surfaces used in extracorporeal circulations result in variable activations of the immune system of complement.
Polymers are widely used for a large range of medical devices used as biomaterials on a temporary... more 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.
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Papers by B. Montdargent