Gaétan Laroche

A study of atmospheric pressure plasma discharges for surface functionalization of PTFE used in biomedical applications

Plasma polymer surface modification is widely used in the biomedical field to tailor the surface properties of materials to improve their biocompatibility. Most of these treatments are performed using low pressure plasma systems but recently, filamentary dielectric barrier discharge (FDBD) and atmospheric pressure glow discharge (APGD) have appeared as interesting alternatives. The aim of this paper is to evaluate the potential of surface modifications realized with FDBD and APGD in different atmospheres (N2+ H2 and N2+ NH3 mixtures) on poly(tetrafluoroethylene) to determine the relative influence of both the discharge regime and the gas nature on the surface transformations. From XPS analysis, it is shown that the discharge regime can have a significant effect on the surface transformation; FDBDs operating in H2/N2 lead to a high concentration of amino-groups with high specificity but also important damaging on the surface. Glow discharges in both H2/N2 and NH3/N2 lead to lower concentrations of amino-groups with lower specificity but lower surface damaging. Therefore, this simple surface treatment seems to be an effective, low cost method for the production of uniform surface modification with amino-groups that can subsequently be used to graft various chemical functionalities used for biomaterial compatibility.

Effects of chemical composition and the addition of H2 in a N2 atmospheric pressure dielectric barrier discharge on polymer surface functionalization.

We examined the effect of hydrogen content in various polymers in a N2/H2 discharge for surface amine functionalization. Three polymers (polyethylene (PE), polyvinylidene fluoride (PVDF), and poly(tetrafluoroethylene) (PTFE)) containing various amounts of hydrogen and fluorine were treated with an atmospheric pressure dielectric barrier discharge (DBD). While surface modification was observed on the PE and the PVDF in a pure N2 discharge, adding H2 in a N2 discharge was necessary to observe the fluorine etching on the surface of the PVDF and PTFE polymers. The presence of a slight amount of hydrogen in the gas mixture was also a prerequisite to the formation of amino groups on the surface of all three polymers (max NH2/C approximately 5%). Aging revealed that the modified polymer surfaces treated in a N2-H2 discharge were less prone to hydrophobic recovery than were surfaces treated in pure N2, due primarily to the presence of a higher density of polar groups on the surfaces. We demonstrated that H atoms in the discharge are necessary for the surface amine functionalization of polymers in a N2 atmospheric pressure DBD, regardless of polymer chemical composition. It is therefore possible to control the plasma functionalization process and to optimize the concentration and specificity of NH2 grafted onto polymer surfaces by varying the H2 concentration in a N2 atmospheric pressure DBD.

On the ability of imatinib mesylate to inhibit smooth muscle cell proliferation without delaying endothelialization: An in vitro study

Restenosis, the re-occlusion of a diseased vessel following a surgical intervention, is a major cause of failure of angioplasty, stenting, and bypass grafting with natural and synthetic vessels. In healthy vessels, the endothelium exerts a control over smooth muscle cell (SMC) proliferation and migration. Unfortunately, revascularization procedures damage the endothelium of natural vessels and bypass vessels are completely devoid of endothelial cells. Many strategies have been developed to inhibit SMC proliferation and reduce intimal hyperplasia, yet most of the drugs tested thus far simultaneously inhibit endothelialization and do not selectively target SMCs. The ideal biological agent should have anti-proliferative effects on SMCs while preserving vascular healing and endothelialization so as to prevent late thrombosis. Imatinib mesylate is a specific inhibitor of three tyrosine kinase receptors, two of which, PDGF-R and c-Kit, are implicated in the pathogenesis of intimal hyperplasia. In this study, we investigated in vitro the potential of imatinib mesylate to inhibit SMCs and its effect on ECs. Our findings indicate that low doses of imatinib mesylate successfully inhibit SMC proliferation. Furthermore, at these concentrations, the drug was not only harmless to ECs, but also enhanced their proliferation. In light of these in vitro results, imatinib mesylate shows potential as a good candidate to inhibit intimal hyperplasia without delaying neo-endothelialization.

Engineering Biomaterials Surfaces Using Micropatterning

A new technique for micropatterning surfaces for cell growth support is described and characterized. This technique allows covering of large three-dimensional surfaces at low cost with controllable micropatterns. This method takes advantage of the random properties of aerosols and the principles of liquid atomization. Parameters of interest were the pressure of atomization air, the flow rate and volume of the atomised liquid, and the distance between the spray nozzle and the surface of the sample. The experimental setup permitted to obtain mean diameters of spots between 10 and 20 microns with a maximum surface coverage of 20%. In an initial step, polytetrafluoroethylene (PTFE) films were treated with ammonia plasma to insert amino groups on the surface. The ammonia plasma treated films were immersed in a solution containing sulfosuccinimidyl 4-(N-maleidomethyl)cyclohexane-1-carboxy-late (SSMCC) to permit the introduction of maleimido groups on the PTFE surface to subsequently conjugate peptides through a sulfhydryl containing N-terminal cystein residue. Plasma/S-SMCC pretreated surfaces were then sprayed with peptide sequences CGRGDS and CWQPPRARI. Our data showed that spots of CGRGDS peptides over a background of CWQPPRARI peptides were the most effective combination to enhance endothelialization.

Infrared optical actinometry to determine N- and H-atom density in a N2–H2 microwave discharge

Infrared (IR) emission spectroscopy was performed on N2?+?H2 microwave discharges at pressures ranging between 300 and 3000?mTorr. The relative atomic density of N and H was measured by optical actinometry in the IR region at various total gas pressures. The effect of relative hydrogen partial pressure (between 10 and 90% in the discharge) on N and H relative density was also investigated. Although rarely studied, optical actinometry in the IR region has nevertheless provided numerous advantages over traditional techniques performed in the UV?visible (UV?VIS) spectral region. Results show that despite the decrease in the radiative state of the N and H atoms as a function of pressure, their ground state density increased. With increased relative hydrogen concentration under constant pressure, both the ground and the radiative state density of the H atoms increased similarly to that recorded by actinometry, whereas those of the N atoms decreased as expected. In comparing the results of the H-atom density measured in the well-documented UV?visible region and the IR region, optical actinometry confirms the accuracy of the IR method.

Micropatterning Polymer Materials to Improve Endothelialization

Several studies have shown that 65 % of expanded poly (tetrafluoroethylene) (ePTFE) vascular prostheses had to be explanted within 10 years of implantation in humans. The reasons for these explantations relied on thrombosis formation and poor hemocompatibility of synthetic polymers. It has been shown that surface modification of ePTFE arterial prostheses could enable their endothelialization therefore improving their biocompatibility and hemocompatibility. Indeed, endothelial cells naturally cover the biological blood vessel wall and consequently, an endothelial layer constitutes the best achievable hemocompatible surface. In this context, our strategy consisted in micropatterning cell adhesion (RGD) and proliferation (WQPPRARI) peptides on the surface of plasma-functionalized PTFE, therefore enabling covalent conjugation of the peptides. Basically, the technology consisted in spraying a solution of the adhesion peptide, therefore leading to 10 µm-diameter RGD spots semi-randomly distributed over the sample and covering 20 % of the whole polymer surface. In a second step, proliferation peptide was applied to the remaining surface by soaking, therefore covering the unreacted surface. The 20 % coverage was obtained by using an x-y table, programmed to move from side to side of the surface on x value, with an increment on y value that has been calibrated.