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Biomedical subjects

G Laroche

Publications and source records attributed to G Laroche.

At least 19 recordsLinked to original sources

Development of an optimized electrochemical process for subsequent coating of 316 stainless steel for stent applications.

Metallic endovascular stents are used as medical devices to scaffold biological lumen, most often diseased arteries, after balloon angioplasty. They are commonly made of 316L stainless steel or Nitinol, two alloys containing nickel, an element classified as potentially toxic and carcinogenic by the International Agency for Research on Cancer. Although they are largely implanted, the long-term safety of such metallic elements is still controversial, since the corrosion processes may lead to the release of several metallic ions, including nickel ions in diverse oxidation states. To avoid metallic ion release in the body, the strategy behind this work was to develop a process aiming the complete isolation of the stainless steel device from the body fluids by a thin, cohesive and strongly adherent coating of RF-plasma-polymerized fluoropolymer. Nevertheless, prior to the polymer film deposition, an essential aspect was the development of a pre-treatment for the metallic substrate, based on the electrochemical polishing process, aiming the removal of any fragile interlayer, including the native oxide layer and the carbon contaminated layer, in order to obtain a smooth, defect-free surface to optimize the adhesion of the plasma-deposited thin film. In this work, the optimized parameters for electropolishing, such as the duration and the temperature of the electrolysis, and the complementary acid dipping were presented and accurately discussed. Their effects on roughness as well as on the evolution of surface topography were investigated by Atomic Force Microscopy, stylus profilometry and Scanning Electron Microscopy. The modifications induced on the surface atomic concentrations were studied by X-ray Photoelectron Spectroscopy. The improvements in terms of the surface morphology after the pre-treatment were also emphasized, as well as the influence of the original stainless steel surface finish.

Coated Materials, Biocompatible↗

Improving arterial prosthesis neo-endothelialization: application of a proactive VEGF construct onto PTFE surfaces.

The formation of a confluent endothelium on expanded polytetrafluoroethylene (PTFE) vascular prostheses has never been observed. This lack of endothelialization is known to be one of the main reasons leading to the development of thromboses and/or intimal hyperplasia. In this context, several efforts were put forward to promote endothelial cell coverage on the internal surface of synthetic vascular prostheses. The goal of the present study was to immobilize the vascular endothelial growth factor (VEGF) onto Teflon PTFE surfaces to generate a proactive polymer construct favoring interaction with endothelial cells. An ammonia plasma treatment was first used to graft amino groups on PTFE films. Subsequent reactions were performed to covalently bind human serum albumin (HSA) on the polymer surface and to load this protein with negative charges, which allows adsorbtion of VEGF onto HSA via strong electrostatic interactions. X-ray photoelectron spectroscopy (XPS) experiments along with surface derivatization strategies were performed between each synthesis step to ascertain the occurrence of the various molecules surface immobilization. Finally, the electrostatic binding of VEGF to the negatively charged HSA matrix was performed and validated by ELISA. Endothelial cell adhesion and migration experiments were carried out to validate the potential of this VEGF-containing biological construct to act as a proactive media toward the development of endothelial cells.

Adsorption↗

Understanding the biodegradation of polyurethanes: from classical implants to tissue engineering materials.

After almost half a century of use in the health field, polyurethanes (PUs) remain one of the most popular group of biomaterials applied for medical devices. Their popularity has been sustained as a direct result of their segmented block copolymeric character, which endows them with a wide range of versatility in terms of tailoring their physical properties, blood and tissue compatibility, and more recently their biodegradation character. While they became recognized in the 1970s and 1980s as the blood contacting material of choice in a wide range of cardiovascular devices their application in long-term implants fell under scrutiny with the failure of pacemaker leads and breast implant coatings containing PUs in the late 1980s. During the next decade PUs became extensively researched for their relative sensitivity to biodegradation and the desire to further understand the biological mechanisms for in vivo biodegradation. The advent of molecular biology into mainstream biomedical engineering permitted the probing of molecular pathways leading to the biodegradation of these materials. Knowledge gained throughout the 1990s has not only yielded novel PUs that contribute to the enhancement of biostability for in vivo long-term applications, but has also been translated to form a new class of bioresorbable materials with all the versatility of PUs in terms of physical properties but now with a more integrative nature in terms of biocompatibility. The current review will briefly survey the literature, which initially identified the problem of PU degradation in vivo and the subsequent studies that have led to the field's further understanding of the biological processes mediating the breakdown. An overview of research emerging on PUs sought for use in combination (drug + polymer) products and tissue regeneration applications will then be presented.

Absorbable Implants↗

Fourier transform infrared spectroscopy application to vascular biology: comparative analysis of human internal mammary artery and saphenous vein wall.

Saphenous vein (SV) and internal mammary artery (IMA) are used for aorto-coronary bypass grafting. IMA is considered to be the graft of choice for coronary revascularization having a long-term patency compared to SV. The aim of this study is to investigate the structure of vascular wall using a new technical approach. We analysed the chemical composition of vessel wall layers (total lipid, lipid ester and protein) of 25 vascular segments (19 SV and 6 IMA) using Fourier transform infrared spectroscopy (FTIR). FTIR analysis showed that in intima layer lipid ester and protein concentration (expressed as arbitrary units) was significantly higher in SV (lipid ester = 0.020 +/- 0.002; protein = 0.449 +/- 0.022) than in IMA (lipid ester = 0.014 +/- 0.002; protein = 0.342 +/- 0.032). Moreover, the percentage of lipid ester on total lipid was significantly higher in SV (intima = 54.7 +/- 2.9%; media = 78.4 +/- 4.9%; adventitia = 83.9 +/- 8.3%) wall layers compared to IMA ones (intima = 37.3 +/- 4.9%; media = 45.4 +/- 3.8; adventitia = 57.1 +/- 4.8). These data suggest that a different chemical composition of wall layers could also be responsible for the morphological modifications observed in SV after grafting.

Aged↗

Modeling lipid uptake in expanded polytetrafluoroethylene vascular prostheses and its effects on mechanical properties.

The radial transport across the wall of expanded polytetrafluoroethylene (ePTFE) arterial prostheses has a significant effect on lipid uptake observed in prostheses implanted in humans, which has been postulated to be one of the causes associated with implant failure. The goal of this study was to stimulate radial transport on a lipidic dispersion across the wall of an ePTFE prosthesis and investigate its effects on the circumferential mechanical properties of the prosthesis. An in vitro model was developed to simulate the lipidic radial transport across the wall. Lipids contained in a phosphatidylcholine dispersion were used as the transported molecules. Lipid concentration profiles were obtained after exposing commercial ePTFE prostheses to various transmural pressure and/or lipidic concentration gradients. Phospholipids gradually accumulated up to the external reinforcing wrap of the prosthesis, which clearly acted as a rigid barrier against lipid infiltration. Tensile tests performed on the virgin samples showed that the wrap was much more rigid than the microporous part of the prosthesis. After the lipid simulation, the rigidity of the wrap decreased with respect to what was observed for the virgin prosthesis. Finally, some clinical implications of this phenomena are discussed.

Biocompatible Materials↗

Totally implantable artificial hearts and left ventricular assist devices: selecting impermeable polycarbonate urethane to manufacture ventricles.

In the development of a new generation of totally implantable artificial hearts and left ventricular assist devices (VADs) for long-term use, the selection of an acceptable material for the fabrication of the ventricles probably represents one of the greatest challenges. Segmented polyether urethanes used to be the material of choice due to their superior flexural performance, acceptable blood compatibility, and ease of processing. However, because they are known to degrade and to be readily permeable to water, they cannot meet the rigorous requirements needed for a new generation of implantable artificial hearts and VADs. Therefore, the objective of the present study was to identify alternative polymeric materials that would be satisfactory for fabricating the ventricles, and in particular, to determine the water permeability through membranes made from four commercial polycarbonate urethanes (Carbothane PC3570A, Chronoflex AR, Corethane 80A, and Corethane 55D) in comparison to those made from two traditional polyether urethanes (Tecoflex EG80A and Tecothane TT-1074A). In addition to determining the rate of water transmission through the six membranes by exposing them to deionized water, saline, and albumin-Krebs solution under pressure and measuring the displacement of liquid by means of a recently developed capillary method, the inherent surface and chemical properties of the six membranes were characterized by SEM, contact angle measurements, FTIR, DSC, and GPC techniques. The results of the study demonstrated that the rate of water transmission through the four polycarbonate urethane membranes was significantly lower than through the two polyether urethanes. In fact the lowest values were recorded with the two Corethane membranes, and the harder type 55D polymer had a lower value (2.7 x 10(-7) g/s cm2) than the softer 80A version (3.3 x 10(-7) g/s cm2). This level of water vapor permeability, which appears to be controlled primarily by a Fickian diffusion mechanism, is between 2 and 4 times lower than that obtained with traditional polyether urethane membranes of equivalent thickness. The superior performance of the polycarbonate urethanes is likely due to the inherently lower chain mobility of the carbonate structure in the soft segment phase. In addition, the study shows that additional impermeability to water vapor can be achieved by selecting a polyurethane polymer with a high hard segment content, an aromatic rather than aliphatic diisocyanate comonomer, and a more hydrophobic surface. The use of a higher molecular weight polyurethane is not necessarily efficacious if the above requirements are not met. As expected by Raoult's Law, the study found that the use of physiological media instead of deionized water further decreases the rate of water vapor transmission. Because none of today's commercial polyurethanes are totally impervious to water vapor transmission, additional work is needed to develop permeable polymers or to apply additional treatments to existing candidates to achieve an acceptable impermeable ventricle material.

Biocompatible Materials↗

A new generation of polyurethane vascular prostheses: rara avis or ignis fatuus?

Three polyurethane (PU) vascular grafts with novel designs were investigated and compared in terms of the microporous structure, reinforcement technology, polymer chemistry, microphase separation, and mechanical properties. The Corvita graft, composed of a poly(carbonate urethane) polymer, displayed a helically wound filament structure with communicating inter-fiber spaces. The reinforced model contained an external PET mesh impregnated with a protein sealant, and displayed good microphase separation, the highest Young's modulus in the longitudinal direction, and the second highest in the radial direction. The Thoratec graft was made of a polyetherurethaneurea with an average micropore size of 15 microns. Silicone was observed on both surfaces of the graft. The Thoratec device displayed a low degree of hydrogen-bonding among the urethane groups and had no well-organized hard-segment domains. Its mechanical strength was superior to that of the Pulse-Tec graft. A solid PU layer underneath the luminal surface precluded any communication between the luminal and adventitial sides. The Pulse-Tec prosthesis was composed of polyetherurethane, with an average micropore size of 28 microns. It offered the highest radial compliance, a high degree of hydrogen-bonding, a narrow molecular weight distribution, and a certain degree of microphase separation. Its tensile strength and hysteresis loss were inferior to those of the other two grafts.

Animals↗

Lipid uptake across the wall of an expanded polytetrafluoroethylene vascular graft.

Previous studies have shown that vascular grafts were prone to inducing an atherosclerosis-like phenomenon, thus possibly jeopardizing their performance. Furthermore, lipid retention, observed in most synthetic arterial prostheses explanted from humans, appears to have an important role in the progression of this atherosclerotic process, therefore hindering the healing process and neo-intima formation of these synthetic conduits. The current study examined lipid concentration profiles across prosthesis membranes exposed to lipid dispersion under various transmural pressures, flow rates, and durations of exposure. It was demonstrated that the lipids rapidly permeated the prosthesis membrane, as lipid advection increased to a maximum, then steadily decreased until the membrane became completely impermeable to the fluid. The concentration of lipids within the grafts was monitored using FT-IR microspectroscopy, then correlated as a function of time in order to evaluate the mass transfer coefficients and lipid saturation concentration. Lipid sorption, as a function of time, was described by a mechanism taking into account two first-order kinetic models. The lipids were first rapidly adsorbed onto the Teflon(R), potentially influenced by the strong affinity of these lipids for the highly hydrophobic polytetrafluoroethylene polymer. This affinity then enhanced the germination of the lipid deposits that filled in the prosthesis wall. For lipid retention as a function of the transmural pressure and flow rate, no clear tendency was established.

Bioprosthesis↗

Lipid uptake in synthetic vascular prostheses explanted from humans.

Previous in vivo studies in humans and dogs have revealed an atherosclerosis-like phenomenon in which lipid penetration within arterial prosthesis wall was observed. The primary goal of the present study was therefore to investigate the occurrence of this lipid retention in ePTFE prostheses implanted in humans and therefore identify potential risk factors related to this phenomenon. Lipid uptake in 367 ePTFE microporous vascular prostheses explanted from humans was studied using Fourier transform infrared spectroscopy. The assignment of the infrared absorption features clearly revealed the presence of strongly bonded unsaturated fatty acids to the microporous structure of the prostheses. A one-way ANOVA statistical analysis showed that the lipid uptake in the synthetic vascular prostheses depended on the duration of implantation of the prosthesis and on the sex of the patient. A two-way ANOVA showed that a relationship existed between the estimated lipid uptake and the internal diameter of the prosthesis. These results confirm that the lipid uptake phenomenon depends on some clinical factors related either to the patients or to the prostheses' morphological parameters.

Aged↗

Commercial polyurethanes: the potential influence of auxiliary chemicals on the biodegradation process.

This investigation elucidates some aspects of auxiliary chemicals on the biodegradation of two commercial polyurethanes (Pellethane and Corethane). The materials were incubated for 28 days with cholesterol esterase and/or with phosphatidylcholine. Extraction studies were carried out on the two materials, using different solvents, chosen on the basis of solvent polarity. FT-IR spectra for the extracted materials indicated the presence of poly(methylene)n oxide moities, silicone oil, bis-ethylene-stearamide, aromatic moities, and alkyd-urea compounds in Pellethane. Corethane materials were shown to contain some fatty acids, hydrocarbon waxes, ester-based species, and chlorinated compounds. Analysis of incubation solutions by high performance liquid chromatography failed to isolate methylene dianiline (MDA) or any of its derivatives from the various polymer incubation solutions. However, a methanol extract of Corethane samples that were incubated for 28 days in cholesterol esterase did show the presence of MDA. The absence of MDA in the Pellethane methanol extracted samples may reflect the differences in surface additives found for this material versus the Corethane. FT-IR/ATR analysis of polymer surfaces exposed to cholesterol esterase/phospholipids mixture showed that there was an increase in the uptake of phospholipids over samples that were incubated in phospholipid dispersion alone. The results of this study show that some of the auxiliary chemicals found in commercial polyurethanes may hinder the specific release of hydrolytic degradation products and delay polymer degradation. However, it should be recognized that the surface layer containing these compounds is susceptible to change following the interaction between the polyurethane-based devices and elements of the host environment (i.e. lipids, enzymes, etc.). Hence, recognition and identification of these changes will ultimately be important in assessing a commercial polymer's blood compatibility characteristics.

Biodegradation, Environmental↗

In vitro cellular response to polypyrrole-coated woven polyester fabrics: potential benefits of electrical conductivity.

Electrically conducting polypyrrole-treated films have recently been shown to influence the morphology and function of mammalian cells in vitro. This type of polymer represents a possible alternative biomaterial for use in vascular implantation. The present study compared the in vitro biocompatibility of the five different polyester woven fabrics having increasing levels of electrical conductivity ranging from 4.5 x 10(4) to 123 omega/square with that of low density polyethylene and polydimethylsiloxane primary reference materials. Biocompatibility was measured in terms of four different types of in vitro cellular response, including (a) an indirect and (b) a direct control organotypic culture assay using endothelial cells, (c) a polymorphonuclear (PMN) cell activation study using flow-cytometric measurements of CD11/CD18 integrin molecule expression, and (d) a semiquantification of interleukin (IL)-6 mRNA expression on monocytes/macrophages using reverse-transcriptase polymerase chain reaction. The organotypic culture study revealed that the fabrics with high levels of conductivity exhibited lower cell migration, proliferation, and viability. The PMN activation study of blood from 10 healthy adult donors demonstrated that the two most conductive fabrics were able to identify the more reactive donors. The levels of IL-6 mRNA expression by monocytes/macrophages decreased as the conductivity level of the fabrics increased. The results of the present study therefore indicate that high levels of conductivity (< 200 omega/square) on polyester fabrics are detrimental to the growth, migration, and viability of endothelial cells; induce elevated PMN activation; and affect the intracellular metabolism of monocytes. They also point to a specific range of conductivity (10(3) < 10(4) omega/square) which is associated with an optimum in vitro cellular response.

Adult↗

Lipid concentration profile across the wall of pseudoatherosclerotic synthetic arterial prostheses using FTIR microspectroscopy.

FTIR microscopy is a versatile technique successfully used to probe the subcellular chemical composition of atherosclerostic arterial walls. To design new vascular substitutes that resist lipid uptake (the major cause of the phenomenon referred to as atherosclerosis-like), identifying and understanding lipid distribution within the pseudoatherosclerosed arterial prostheses is of prime importance. Until now, the amount of lipids present within arterial prostheses that had been explanted from either animals (during in vivo trials) or humans (after the failure of vascular grafts) or had been submitted to in vitro investigations could only be measured through the use of histological techniques or radioactive labeling methods. We present here a novel method to quantitatively measure the lipid concentration profile within the wall of arterial prostheses by means of Fourier transform infrared microspectroscopy. Essentially, prostheses are fixed in a 1% osmium tetraoxide aqueous solution under vacuum and radially cut with a 5-micron thickness with a microtome. The sections are then placed onto BaF2 windows and observed with a microscope attached to a FTIR spectrometer with a 30 microns x 50 microns sampling area. The lipid concentration profile is obtained by scanning the prosthesis wall from the inner to the outer surface and reporting the corresponding integrated absorbance between 2700 and 3100 cm(-1) against a calibration curve. The application of this technique constitutes the first quantitative measurement of the concentration of biological molecules within the wall of artificial arterial substitute.

Blood Vessel Prosthesis↗

Identification and quantification of the crystalline structures of poly(vinylidene fluoride) sutures by wide-angle X-ray scattering and differential scanning calorimetry.

The outstanding biocompatibility of the polyvinylidene fluoride (PVDF) monofilament suture together with other desirable characteristics, such as ease of handling and resistance to biodegradation, makes it an attractive alternative monofilament suture material for cardiovascular surgery. However, to achieve a high performance suture, the polymeric raw material must be exposed to different treatments, which lead to different degrees and types of crystallization. Since these crystalline modifications deeply influence the mechanical characteristics and the biostability of the sutures, the authors hereby propose a method of quantifying the different structures of PVDF using wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC). The commercial devices are achieved by coloring and processing the polymeric raw material. The white and unprocessed 4-0 unswaged suture presents 19% of the alpha phase, 38% of the beta structure, and no gamma form. Coloration increases the amount of the beta phase by 5-9% at the expense of the alpha phase. On the other hand, processing the fibers lead to the conversion of some of the amorphous phase to the gamma structure, the importance of which is 6-7%. Finally, tensile measurements performed on the different PVDF fibers clearly proves that their mechanical characteristics depend on the presence of these crystalline forms in the polymeric structure of PVDF.

Calorimetry, Differential Scanning↗

Lipid uptake in expanded polytetrafluoroethylene vascular grafts.

PURPOSE: The mechanisms of vascular prosthesis failure are reported to be associated, in part, with an atherosclerotic degenerative process that is related to an abnormal lipid infiltration. The lipid uptake in expanded polytetrafluoroethylene (ePTFE) vascular grafts was reproduced in vitro, and the effect of time on the permeability of these prostheses was studied. METHODS: Water permeability tests were carried out under dynamic flow conditions at various hydrostatic pressures. Lipid uptake was simulated by circulating a phosphatidylcholine suspension inside an expanded Teflon prosthesis under pulsatile or continuous transmural pressure ranging between 80 mm Hg and 180 mm Hg, at a flow rate of 500 mL/min and 2000 mL/min, for a duration ranging from 2 hours to 1 month. RESULTS: Water permeability tests indicated that under hydrostatic pressures of 180 mm Hg and 300 mm Hg, water percolated through the prosthesis wall after an exposure of 720 minutes and 75 minutes, respectively. After exposing the prostheses to the lipid dispersion under the various flow conditions, the fluid convection through the wall occurred. Preferential convection pathways with a constant periodicity were observed across the length of each prosthesis and were, therefore, associated with regularly spaced perforations depicted in the structure of the devices. Phospholipids gradually agglomerated within the prosthesis wall, allowing a restrictive molecular mobility. Infrared spectroscopy results indicated that the lipid uptake depended on the transmural pressure and time of exposure. CONCLUSION: The occurrence of the membrane permeability may be associated with the dilatation and plastic deformation of the prosthesis. Lipid uptake occurs in ePTFE grafts after an aggressive kinetic process.

Blood Vessel Prosthesis↗

A continuous and pulsatile flow circulation system for evaluation of cardiovascular devices.

The design of a nonpulsatile and pulsatile system using a centrifugal pump is presented. To induce a pulsatile flow with a centrifugal pump, an independent pneumatically driven unit provided flow patterns over a wide range of frequencies and amplitudes. The pulsatile flow was generated by the axial displacement of a cylinder that periodically compressed the flexible conduit that is connected to the pump. The system can accommodate flow rates up to 6,000 ml/min and transmural pressures up to 500 mm Hg and is capable of maintaining the pressure at a constant value. This circuit produced reproducible pressure waves having a frequency up to 4 Hz. The periodicity of the transmural pressure between 80 and 180 mm Hg was similar to the pressure wave propagation observed in peripheral circulation. Capable of adequately reproducing continuous and pulsatile flow, the apparatus is therefore versatile to allow in vitro evaluation of cardiovascular devices.

Centrifugation↗

Heterogeneous PHPMA hydrogels for tissue repair and axonal regeneration in the injured spinal cord.

A biocompatible heterogeneous hydrogel of poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) showing an open porous structure, viscoelastic properties similar to the neural tissue and a large surface area available for cell interaction, was evaluated for its ability to promote tissue repair and axonal regeneration in the transected rat spinal cord. After implantation, the polymer hydrogel could correctly bridge the tissue defect, from a permissive interface with the host tissue to favour cell ingrowth, angiogenesis and axonal growth occurred within the microstructure of the network. Within 3 months the polymer implant was invaded by host derived tissue, glial cells, blood vessels and axons penetrated the hydrogel implant. Such polymer hydrogel matrices which show neuroinductive and neuroconductive properties have the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost of tissue.

Animals↗

Chemical stability of polyether urethanes versus polycarbonate urethanes.

The relative chemical stability of two commercially available polyurethanes-Pellethane, currently used in biomedical devices, and Corethane, considered as a potential biomaterial-was investigated following aging protocols in hydrolytic and oxidative conditions (HOC, water, hydrogen peroxide, and nitric acid) and in physiological media (PHM, phosphate buffer, lipid dispersion, and bile from human donors). The chemical modifications induced on these polymers were characterized using differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and Fourier transform infrared spectroscopy (FTIR). With the exception of nitric acid, all of the aging media promoted a mild hydrolytic reaction leading to a slight molecular weight loss in both polymers. When aged in water and hydrogen peroxide, Pellethane experienced structural modifications through microdomain phase separation along with an increase of the order within the soft-hard segment domains. The incubation of Pellethane in nitric acid also resulted in an important decrease of the melting temperature of its hard segments with chain scission mechanisms. Moreover, incubation in PHM led to an increase of the order within shorter hard-segment domains. FTIR data revealed the presence of aliphatic amide molecules used as additives on the Pellethane's surface. The incubation of Corethane under the same conditions promoted an almost uniform molecular reorganization through a phase separation between the hard and soft segments as well as an increase of the short-range order within the hard-segment domains. Incubation of this polymer in nitric acid also resulted in a chain scission process that was less pronounced than that measured for the Pellethane samples. Finally, lipid adsorption occurred on the Corethane sample incubated in bile for 120 days. Overall data indicate that polycarbonate urethane presents a greater chemical stability than does polyetherurethane.

Calorimetry, Differential Scanning↗