Evaluation du greffage de polymères bioactifs à architectures variées sur la réponse biologique in vitro pour une diminution des infections bactériennes et une amélioration de l’ostéointégration

This work deals with the grafting of polyNaSS (bioactive polymer) to the surface of titanium in order to propose a solution to prevent bacterial infections while promoting the osseointegration of total hip prostheses. The grafting of the polyNaSS is carried out in two ways: a "direct" grafting using the "grafting from" technique and an indirect grafting using the "grafting to" technique. "Direct" grafting uses UV radiation to initiate NaSS polymerisation from the titanium surface. Conversely, "indirect grafting" requires the use of an anchoring molecule - derived from dopamine - which will make the link between the polyNaSS and the surface of the titanium. The advantage of "indirect grafting" is that it is possible to graft polyNaSS chains of defined sizes (5, 10 and 35 kDa) to the surface of the titanium; The polyNaSS chains are synthesised in a controlled manner by a RAFT polymerisation and then coupled to a dopamine derivative by "click" chemistry. However, the coverage of the surface by the polyNaSS is less than that of a "direct" grafting.The titanium surfaces grafted by both techniques were evaluated in vitro to determine their bacterial and osseointegration effects. All grafted surfaces are biocompatible and have no cytotoxicity effect on bone cells. A greater cellular response (osteoblasts) is achieved for the surfaces grafted by "direct" grafting compared to the "indirect" grafting. However, for the bacterial response (Staphylococcus aureus) the response is dependent on the size of the grafted polymer.Ces travaux de recherche traitent du greffage du polyNaSS (polymère bioactif) à la surface du titane dans le but de proposer une solution permettant de prévenir les infections bactériennes tout en favorisant l’ostéointégration des prothèses totales de hanche. Le greffage du polyNaSS est réalisé selon deux voies : un greffage dit «direct» utilisant la technique de «grafting from» et un greffage indirect utilisant la technique de «grafting to». Le greffage «direct» utilise les radiations UV pour amorcer la polymérisation du NaSS à partir de la surface du titane. A l’inverse le «greffage indirect» nécessite l’utilisation d’une molécule d’ancrage - dérivée de la dopamine- qui fera le lien entre le polyNaSS et la surface du titane. L’intérêt du «greffage indirect» est de pouvoir greffer des chaînes de polyNaSS de tailles définies (5, 10 et 35 kDa) à la surface du titane ; les chaînes de polyNaSS sont synthétisés de façon contrôlée par une polymérisation RAFT puis couplées à un dérivé de dopamine par une chimie «click». En revanche le recouvrement de la surface par le polyNaSS est plus faible que lors d’un greffage «direct». Les surfaces de titane greffées selon les deux voies ont été évaluées in vitro pour déterminer leurs effets anti adhérence bactérienne et d’ostéointégration. Toutes les surfaces greffées sont biocompatibles et ne présentent aucun effet de cytotoxicité vis à vis des cellules osseuses. La réponse cellulaire (ostéoblastes) est toujours meilleure pour les surfaces greffées par greffage « direct» par comparaison au greffage «indirect». En revanche pour la réponse bactérienne (Staphylococcus aureus) la réponse est dépendante de la taille du polymère greffé

Evaluation of the grafting of bioactive polymers with varied architecture on the biological reponse in vitro for a reduction of bacterial infections and an increasing in osseointegration

Ces travaux de recherche traitent du greffage du polyNaSS (polymère bioactif) à la surface du titane dans le but de proposer une solution permettant de prévenir les infections bactériennes tout en favorisant l’ostéointégration des prothèses totales de hanche. Le greffage du polyNaSS est réalisé selon deux voies : un greffage dit «direct» utilisant la technique de «grafting from» et un greffage indirect utilisant la technique de «grafting to». Le greffage «direct» utilise les radiations UV pour amorcer la polymérisation du NaSS à partir de la surface du titane. A l’inverse le «greffage indirect» nécessite l’utilisation d’une molécule d’ancrage - dérivée de la dopamine- qui fera le lien entre le polyNaSS et la surface du titane. L’intérêt du «greffage indirect» est de pouvoir greffer des chaînes de polyNaSS de tailles définies (5, 10 et 35 kDa) à la surface du titane ; les chaînes de polyNaSS sont synthétisés de façon contrôlée par une polymérisation RAFT puis couplées à un dérivé de dopamine par une chimie «click». En revanche le recouvrement de la surface par le polyNaSS est plus faible que lors d’un greffage «direct». Les surfaces de titane greffées selon les deux voies ont été évaluées in vitro pour déterminer leurs effets anti adhérence bactérienne et d’ostéointégration. Toutes les surfaces greffées sont biocompatibles et ne présentent aucun effet de cytotoxicité vis à vis des cellules osseuses. La réponse cellulaire (ostéoblastes) est toujours meilleure pour les surfaces greffées par greffage « direct» par comparaison au greffage «indirect». En revanche pour la réponse bactérienne (Staphylococcus aureus) la réponse est dépendante de la taille du polymère greffé.This work deals with the grafting of polyNaSS (bioactive polymer) to the surface of titanium in order to propose a solution to prevent bacterial infections while promoting the osseointegration of total hip prostheses. The grafting of the polyNaSS is carried out in two ways: a "direct" grafting using the "grafting from" technique and an indirect grafting using the "grafting to" technique. "Direct" grafting uses UV radiation to initiate NaSS polymerisation from the titanium surface. Conversely, "indirect grafting" requires the use of an anchoring molecule - derived from dopamine - which will make the link between the polyNaSS and the surface of the titanium. The advantage of "indirect grafting" is that it is possible to graft polyNaSS chains of defined sizes (5, 10 and 35 kDa) to the surface of the titanium; The polyNaSS chains are synthesised in a controlled manner by a RAFT polymerisation and then coupled to a dopamine derivative by "click" chemistry. However, the coverage of the surface by the polyNaSS is less than that of a "direct" grafting.The titanium surfaces grafted by both techniques were evaluated in vitro to determine their bacterial and osseointegration effects. All grafted surfaces are biocompatible and have no cytotoxicity effect on bone cells. A greater cellular response (osteoblasts) is achieved for the surfaces grafted by "direct" grafting compared to the "indirect" grafting. However, for the bacterial response (Staphylococcus aureus) the response is dependent on the size of the grafted polymer

Review of titanium surface modification techniques and coatings for antibacterial applications

International audienc

Grafting of architecture controlled poly(styrene sodium sulfonate) onto titanium surfaces using bio-adhesive molecules: Surface characterization and biological properties

International audienc

Grafting of Bioactive Polymers with Various Architectures: A Versatile Tool for Preparing Antibacterial Infection and Biocompatible Surfaces

International audienceThe aim of this Research Article is to present three different techniques of poly(sodium styrene sulfonate) (polyNaSS) covalent grafting onto titanium (Ti) surfaces and study the influence of their architecture on biological response. Two of them are “grafting from” techniques requiring an activation step either by thermal or UV irradiation. The third method is a “grafting to” technique involving an anchorage molecule onto which polyNaSS synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization is clicked. The advantage of the “grafting to” technique when compared to the “grafting from” technique is the ability to control the architecture and length of the grafted polymers on the Ti surface and their influence on the biological responses. This investigation compares the effect of the three different grafting processes on the in vitro biological responses of bacteria and osteoblasts. Overall outcomes of this investigation confirmed the significance of the sulfonate functional groups on the biological responses, regardless of the grafting method. In addition, results showed that the architecture and distribution of grafted polyNaSS on Ti surfaces alter the intensity of the bacteria response mediated by fibronectin

Reliability of hemostasis biomarkers is affected by time-dependent intra-patient variability

International audienceEssentials Nucleosomes and free DNA are two newly described biomarkers in venous thromboembolism (VTE). Reliability of nucleosomes, plasma free DNA and conventional hemostasis markers were studied. Hemostasis biological parameters vary over a short time-frame in VTE patients. Hemostasis biological parameters also vary over a short time-frame in healthy controls. SUMMARY: Background Previous studies have associated neutrophil-derived circulating nucleosomes and plasma free DNA with venous thromboembolism (VTE). However, there are few data concerning these two biomarkers and no studies have compared the reliability of nucleosomes and plasma free DNA against that of conventional hemostasis markers. Objectives We performed a 3-year prospective study of nucleosomes and plasma free DNA levels in comparison with conventional hemostatic biomarkers and blood cells. Patients/Methods Fifteen healthy controls and 22 randomly selected patients with a history of VTE were followed monthly for 6~months. The reliability of these markers was evaluated by the intraclass correlation coefficient (ICCs). Results and Conclusions In healthy controls and patients, we found a low reliability for nucleosomes and plasma free DNA, with ICCs at 0.538 (95% confidence interval [CI], 0.334-0.764) and 0.091 (95% CI, -0.026-0.328), respectively, in the healthy controls, and at 0.213 (95% CI, 0.042-0.463) and 0.161 (CI 95%, 0.008-0.398) in the patient group. For the conventional hemostasis biomarkers and for blood cells, reliability ranged from poor to good in the healthy volunteers and from poor to acceptable in the patient group. Our study shows for the first time that hemostasis biological parameters spontaneously vary over a short time-frame in VTE patients and, more surprisingly, in normal individuals. The clinical value of such intra-individual variations is currently unknown. This variability might mean reinterpreting diagnostic or prognostic models based on static evaluation of individuals. Studying the intrinsic value of individual patterns of markers' variability is warranted