Biological properties of vascular substitutes based on an original collagenic coating

To enlarge the field of application for polyester vascular prostheses in order to restore small-diameter vessels, original collagenic-based composites have been developed in our laboratory. The polyester knit of standard prostheses has been modified by radiochemical grafting of the Type I collagen-based matrix. In order to check the properties of this new coating, biological tests have been carried out. We noticed that on modified surfaces: fibrinogen adsorption is less important than albumin adsorption; only 50% platelets interact actively with the modified material in comparison with the other materials; the coating is more resistant to enzymatic degradation; and there is partial denaturation of the collagen but this collagen is still specifically recognized by Type I collagen antibody.     

Fabrication of TC4/TiCp New Hip Prosthesis by Laser Cladding

Artificial hip prostheses are commonly utilized in total hip replacement surgeries. However, current single materials like metal, polyethylene, and ceramic do not satisfy the comprehensive performance requirements of prostheses, such as biocompatibility, wear resistance, and toughness. To address these limitations, a new metal–ceramic hip prosthesis which can be prepared by laser cladding technique is proposed. By combining the advantages of metal and ceramic, this prosthesis aims to overcome existing product limitations. A TiCp bioceramic coating is prepared on the TC4 surface, and its microstructure, mechanical properties, and biological characteristics are systematically analyzed. The results show that the TiCp phase is uniformly distributed in the coating. Additionally, dendritic TiCp at the bonding interface results in metallurgical bond between the coating and substrate. The α-Ti phase in the matrix of the TiCp coating helps to enhance its fracture toughness and fatigue strength, while the solid solution of trace C elements in the matrix provides solid solution strengthening. Mechanical tests reveal that the microhardness of the TiCp coating is 2.5 times greater than that of the substrate, and the wear mass is reduced by 89.4%. Finally, the TiCp bioceramic coating is verified to be biocompatible, demonstrating excellent potential for use in hip prostheses.     

Biological behaviour of an endothelial cell line (HPMEC) on vascular prostheses grafted with hydroxypropylgamma-cyclodextrine (HPγ-CD) and hydroxypropylbeta-cyclodextrine (HPβ-CD)

The cytocompatibility of cyclodextrins (CDs) grafting on vascular polyester (PET) prostheses for further loading with biomolecules was investigated in this study. Viability tests demonstrated no toxicity of HP-CDs and PolyHP-CDs at 4,000 mg/l with survival rates of 80 to 96%. Proliferation tests using the human pulmonary microvascular endothelial cell line (HPMEC-ST1) revealed an excellent biocompatibility for Melinex (Film form of PET). For Polythese and Polymaille, a good proliferation rate was observed at 3 days (60-80%) but decreased at 6 days (56-73%). For all CD-grafted samples, low proliferation rates were observed after 6 days (35-38%). Vitality tests revealed excellent functional capacities of HPMEC cells after 3 and 6 days for all samples. Adhesion kinetics tests showed a similar adhesion of HPMEC cells on control and Melinex. A low adhesion was observed on Polythese and especially on Polymaille compared to control. After CD grafting, the cell adhesion was decreased. The woven or knitted architecture and CD grafting were the most likely causes of this weak adhesion. The adhesion kinetic test was confirmed by SEM observations and immunocytochemistry. The low proliferation of HPMEC on virgin prostheses and especially on grafted prostheses was not due to a cytotoxic effect, but to the physical surface characteristics of the prostheses.     

Sustained release of antibiotic from polyurethane coated implant materials

Implant associated infections are of increasing importance. To minimize the risks of implant-associated infections recent biomedical strategies have led to the modification of the medical device surfaces. The modifications are in the terms of increasing surface biocompatibility and decreasing bacterial adherence, which can be achieved by applying a coating of biocompatible polymer onto the said surfaces. Entrapping anti-infective agents in a polymer matrix provides an approach to kill bacteria and combat the possibility of any residual infection. We have prepared a biodegradable polyester urethane coat for implant materials, which have the property to accommodate antibiotics within itself. These polyurethane coating materials were characterized by FTIR spectroscopy, swelling property in SBF, gravimetric analysis, drug release, and biocompatibility study. Drug release rates, bacterial colonization and morphological features were also evaluated to predict and understand the antimicrobial activity of these delivery systems. Drug release characteristics were investigated and the physico-chemical mechanisms of the delivery were discussed. Results suggest that the polyester urethane can be used as an implant coating material and can be used as a matrix for the sustained delivery of anti-infective agent.     

Sustained release of antibiotic from polyurethane coated implant materials

Implant associated infections are of increasing importance. To minimize the risks of implant-associated infections recent biomedical strategies have led to the modification of the medical device surfaces. The modifications are in the terms of increasing surface biocompatibility and decreasing bacterial adherence, which can be achieved by applying a coating of biocompatible polymer onto the said surfaces. Entrapping anti-infective agents in a polymer matrix provides an approach to kill bacteria and combat the possibility of any residual infection. We have prepared a biodegradable polyester urethane coat for implant materials, which have the property to accommodate antibiotics within itself. These polyurethane coating materials were characterized by FTIR spectroscopy, swelling property in SBF, gravimetric analysis, drug release, and biocompatibility study. Drug release rates, bacterial colonization and morphological features were also evaluated to predict and understand the antimicrobial activity of these delivery systems. Drug release characteristics were investigated and the physico-chemical mechanisms of the delivery were discussed. Results suggest that the polyester urethane can be used as an implant coating material and can be used as a matrix for the sustained delivery of anti-infective agent.     

Novel fatty acid gentamicin salts as slow-release drug carrier systems for anti-infective protection of vascular biomaterials

Infections of vascular prostheses are still a major risk in surgery. The current work presents an in vitro evaluation of novel slow release antibiotic coatings based on new gentamicin fatty acid salts for polytetrafluoroethylene grafts. These grafts were coated with gentamicin sodium dodecyl sulfate, gentamicin laurate and gentamicin palmitate. Drug release kinetics, anti-infective characteristics, biocompatibility and haemocompatibility of developed coatings were compared to commercially available gelatin sealed PTFE grafts (SEALPTFE?) and knitted silver coated Dacron(?) grafts (InterGard(?)). Each gentamicin fatty acid coating showed a continuous drug release in the first eight hours followed by a low continuous release. Grafts coated with gentamicin fatty acids reduced bacterial growth even beyond pathologically relevant high concentrations. Cytotoxicity levels depending on drug formulation bringing up gentamicin palmitate as the most promising biocompatible coating. Thrombelastography studies, ELISA assays and an amidolytic substrate assay confirmed haemocompatibility of developed gentamicin fatty acid coatings comparable to commercially available grafts.     

Biodegradable poly(lactide-co-glycolide) coatings on magnesium alloys for orthopedic applications

Polymeric film coatings were applied by dip coating on two magnesium alloy systems, AZ31 and Mg4Y, in an attempt to slow the degradation of these alloys under in vitro conditions. Poly(lactic-co-glycolic acid) polymer in solution was explored at various concentrations, yielding coatings of varying thicknesses on the alloy substrates. Electrochemical corrosion studies indicate that the coatings initially provide some corrosion protection. Degradation studies showed reduced degradation over 3 days, but beyond this time point however, do not maintain a reduction in corrosion rate. Scanning electron microscopy indicates inhomogeneous coating durability, with gas pocket formation in the polymer coating, resulting in eventual detachment from the alloy surface. In vitro studies of cell viability utilizing mouse osteoblast cells showed improved biocompatibility of polymer coated substrates over the bare AZ31 and Mg4Y substrates. Results demonstrate that while challenges remain for long term degradation control, the developed polymeric coatings nevertheless provide short term corrosion protection and improved biocompatibility of magnesium alloys for possible use in orthopedic applications.     

Development of an elastomer coated hip prosthesis

A cementless stem for a total hip replacement (THR) was designed aiming at some mechanical advantages of a cemented stem. It is called elastomer coated prosthesis (ECP) and has a metal core, coated with an elastomer layer as a mechanical buffer between the core and the femoral cortex. For the ECP coating a thermoplastic polyolefin elastomer (TPO) was chosen. Required implant sizes were determined from a measurement campaign on the intramedullar canal of German Shepherds' femora. Stress distribution in photo-elastic models of the ensemble ECP core and TPO coating was studied and compared to a model of a cementless system. The core was tested for fatigue resistance in a simulator.Extensive in vitro testing of all ECP components (both core and elastomer coating) has shown that the prosthesis is mechanically suitable for its application. Animal testing was limited to a strict minimum for ethical reasons. Only after obtaining sufficient evidence for biocompatibility in vitro, the elastomer was studied in vivo. Implantation of non-loaded TPO samples in dogs has shown acceptable behaviour in contact with bone and marrow. ECP prototypes are currently being implanted in German Shepherds and post mortem histology will have to deliver final proof of this concept's validity.     

Improvement of adhesion of fucoidan on polyethylene terephthalate surface using gas plasma treatments

Attachment of polysaccharide fucoidan to the polyethylene terephthalate (PET) polymer surface was studied by X-ray photoelectron spectroscopy (XPS). Fucoidan has antithrombogenic and anticoagulant properties and is therefore a promising coating for vascular graft implants for improving their hemocompatibility. Samples of PET polymer were first modified by nitrogen plasma treatment in order to change the surface wettability and to introduce amino groups to the surface, which act as a linker for further binding of fucoidan. Plasma treated samples were then incubated for 30 min in fucoidan solution. The presence of fucoidan layer on the polymer surface was demonstrated by appearance of S2p signal in the XPS spectra of the coated PET samples. The procedure for immobilization of fucoidan on PET surface was optimized by varying pH value of fucoidan solution from 5 to 7.4. The best results were obtained when using lower pH value pH = 5. At these conditions the thickness of the fucoidan coating was estimated to about 7 nm.     

The influences of poly(lactic-co-glycolic acid) (PLGA) coating on the biodegradability, bioactivity, and biocompatibility of calcium silicate bioceramics

Calcium silicate (CaSiO₃) bioceramics and polyesters have complementary qualities as potential bone substituted materials. In this study, sintered CaSiO₃ bioceramics were prepared and coated with poly(lactic-co-glycolic acid) (PLGA), and the influences of the PLGA coating on the degradation, hydrophilicity, bioactivity, and biocompatibility of CaSiO₃ ceramics were investigated. The results showed that the degradation rate was reduced, while hydrophilicity was decreased with the increase of the polymer coating. In addition, the polymer coating resulted in a decrease of the alkaline pH value during the degradation of the ceramics, which indicated an increase of the cell biocompatibility, confirmed by the attachment and proliferation of rMSCs on the surface of the polymer-coated ceramics. Furthermore, the apatite-forming ability of the PLGA-coated CaSiO₃ bioceramics was maintained. This study suggested that the coating with PLGA might be a useful method to improve the integrative properties of CaSiO₃ bioceramics for applications in bone regeneration and bone tissue engineering.     

In vitro study of drug-eluting stent coatings based on poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) incorporating cyclosporine A – drug release,polymer degradation and mechanical integrity

In this study, absorbable polymer stent coatings for localized drug delivery based on poly(l-lactide) (PLLA) and cyclosporine A (CsA) were developed and tested in vitro. Metallic stents were coated with different compositions of PLLA/CsA (70/30, 60/40, 50/50% w/w) and β-sterilized. The specimens were used to assess the drug release kinetics with HPLC. Sterilization influenced polymer degradation was measured with GPC. Mechanical integrity of the stent coatings was studied with SEM. The interconnection of the coated stents with a balloon-catheter was characterized by the measurement of stent dislodgment force. A migration assay was used to determine the inhibitory effect of the model drug CsA on smooth muscle cell (SMC) migration. The release of CsA was established over time periods up to 24 days in sodium chloride solution and in porcine blood plasma. An inhibition of SMC migration (max. 26–33%) was found for CsA concentrations of 4 × 10⁻⁵ to 4 × 10⁻⁷ mol/l. Marked molecular weight reduction (70–80%) of the PLLA matrix occurred after β-sterilization. We also observed a substantial decrease of in vitro degradation time. The maintenance of the mechanical integrity of the polymer coating during crimping and dilation of the specimens could be verified, and a sufficient stent dislodgment force of 0.8–0.9 N was measured.     

Endothelial cell compatibility testing of various prosthetic surfaces

Numerous methods are proposed to reduce the surface thrombogenicity of vascular prostheses, among them endothelialization of the lumen which has had clinical application since 1985. One of the problems is to collect enough cells to rapidly obtain a complete monolayer at the time of implantation. Thus, material improvements are necessary to enhance cell adhesion and spreading. A collaboration with the Bakoulev Institute (Moscow) gave us the opportunity to study the cytocompatibility of carbon coated materials (PAN and Vitlan^®), polyester coated with albumin and/or synthetic polysaccharide. Studies were carried out with cultured human umbilical vein endothelial cells (HUVEC). Two steps are distinguished: indirect tests (medium added with materials extracts), then direct tests (cells directly seeded onto materials). Neither PAN, Vitlan^® nor polyesters extracts have provoked a toxic effect on HUVEC. Concerning attachment on materials, a maximum of 60% of seeded cells is reached. Cells could proliferate and confluency is obtained between days 5 and 10 for the best materials. SEM corroborated these results. On polysaccharide-coated polyester (M. 11), HUVEC produced significant levels of vWF after thrombin stimulation (ELISA assay): vWF was functional (ristocetin cofactor activity). In conclusion, PAN and M. 11 gave encouraging results and further studies remain to be investigated.     

Inorganic materials as drug delivery systems in coronary artery stenting

Recent studies proved coronary stent implantation to be superior over conventional angioplasty in the treatment of coronary artery disease. However, restenosis remains one of the most crucial problems in interventional cardiology. Inflammatory infiltrates and foreign body reactions can be found in the tissue surrounding the struts in stenting. Thrombogenesis, proliferation of α‐actin expressing cells (smooth muscle cells) and hyperplasia of the intima occur. In order to improve the biocompatibility of the stents, new stent designs and stent coatings have been developed. One advantage of stent coating is the combination of mechanical stability of the stent with the biocompatibility of the coating. The coatings are divided into active and passive coatings. Passive coatings improve the biocompatibility of the stent, while active coatings may suppress neointima proliferation by releasing anti‐inflammatory or antiproliferative substances. Immunosuppressive drugs (tacrolimus, sirolimus) and cytostatic drugs (paclitaxel) have been tested in several studies and showed promising results. However, it could also be demonstrated that polymer‐coated stents used as a matrix for drug release reduced the hyperplasia of the intima. However, after dissipation of the immunosuppressants or cytostatics, the presence of the polymer itself lead to a delayed inflammation and proliferation causing restenosis. Thus, efforts have been made to develop inorganic coatings that are suitable for drug loading. One promising approach is a new nanoporous alumina coating. Preliminary tests with this coating revealed favourable loading characteristics and sustained drug release in vivo. The present article provides an overview on different approaches for stent coatings.     

Strain-sensitive Raman spectroscopy and electrical resistance of carbon nanotube-coated glass fibre sensors

This paper presents the development of glass fibres coated with nanocomposites consisting of carbon nanotubes (CNTs) and epoxy. Single glass fibres with different CNT content coating are embedded in a polymer matrix as a strain sensor for composite structures. Raman spectroscopy and electrical response of glass fibres under mechanical load are coupled for in situ sensing of deformation in composites. The results show that the fibres with nanocomposite coating exhibit efficient stress transfer across the fibre/matrix interface, and these with a higher CNT content are more prone to fibre fragmentation at the same matrix strain. A relationship between the fibre stress and the change in electrical resistance against the fibre strain is established. The major finding of this study has a practical implication in that the fibres with nanocomposite coating can serve as a sensor to monitor the deformation and damage process in composites.     

Lipid uptake in ePTFE arterial prostheses implanted in humans

Lipid uptake in 104 ePTFE microporous vascular prostheses implanted in humans was investigated using Fourier transform infrared (FTIR) spectroscopy. The assignment of the infrared features observed in the spectra of explanted ePTFE microporous vascular prostheses shows unambiguously the presence of fatty acids in the structure of the arterial prosthesis wall. In addition, higher lipid concentration is found on the external side of the prostheses before 500 days of implantation, after which this behaviour is reversed. Finally, it seems that a greater amount of lipids are present on the surfaces of prostheses implanted in extra-anatomical sites as compared to those implanted in anatomical sites.     

Effect of the solubility of antibiotics on their release from degradable polyurethane

Application of biodegradable polyester urethane, as a drug loading matrix in the form of a coating on implant devices was investigated. Polyester urethane films were loaded with model antibiotics, like rifampicin, gentamicin and ciprofloxacin and their release characteristics were evaluated in simulated body fluid. Effect of solubility of antibiotics and degradation of matrix on the drug release behavior of biodegradable polyester urethane coating was also studied. It was observed that antibiotics having hydrophilicity or lipophilicity same as that of polymer matrix provide an extended release with relatively less initial burst release. Effect of degradation of polymer matrix has a dual significance in this case and the drug release rate increases with the increase in degradation rate. A high initial burst release was observed for antibiotics having hydrophilicity or lipophilicity opposite to that of polyurethane matrix and hence in this case antibiotic release was not significantly controlled by degradation of matrix.     

Short-and long-term neural biocompatibility of heparin coated sapphire implants

Sapphire is one of the most promising materials for the development of implantable biomedical devices due to its exceptional chemical, mechanical, electrical, thermal and optical properties. Silicon has also been widely used to manufacture neuroprosthetic devices in the past. However, both of these materials have been found to cause the most severe tissue reactions while implanted in vivo in the rat brain, compared with other biomaterials. In order to enhance the biocompatibility of sapphire and silicon, their surfaces were modified by depositing a self-assembled monolayer (SAM) of octadecyltrichlorosilane (OTS), followed by the photo-immobilization of heparin. To comprehensively evaluate the short- and long-term neural biocompatibility, sapphire and silicon wafers (2.5 mm dia × 0.25 mm thick) with and without heparin coating were implanted on the surface of adult rat's cortex for 10, 28 and 90 days. Specific evaluations of the cell types that contribute to an inflammatory response were performed. The histological results indicate that the biocompatibility of sapphire is dramatically improved by heparin immobilization, while this dramatic improvement is not observed on heparin coated silicon. The failure to improve the biocompatibility of silicon by heparin immobilization can be attributed to the corrosion of the silicon surface in vivo, which was confirmed by atomic force microscopy (AFM). Meanwhile, no corrosion was observed on heparin coated sapphire surfaces and a very thin layer of proteins or extracellular matrix was deposited on the surfaces.     

Peptide-coated vascular grafts: An in vivo study in sheep

The data on function and patency of prosthetic vascular grafts in various clinical settings are limited. The purpose of this in vivo study was to compare the function and patency of P15‐coated expanded polytetrafluoroethylene (ePTFE) vascular grafts to uncoated ePTFE grafts in sheep. The P15 cell‐binding peptide was covalently immobilized onto the surface of ePTFE grafts by a novel atmospheric plasma coating method. We evaluated the amount of neointimal tissue ingrowth present at the arterial and venous sides of the anastomoses and the degree of endothelial cell resurfacing of the luminal surface of the graft. Four P15‐coated grafts and two control grafts were implanted as arteriovenous grafts between the femoral artery and vein and the carotid artery and jugular vein in two sheep (n = 6). One animal was euthanized after 14 days and the other after 28 days. The study showed the intimal ingrowth was significantly less. The average intimal thickness of P15‐coated grafts (658 µm) was approximately two and a half times less than that of uncoated samples (1657 µm). The newly formed endothelial cell lining was thicker and its coverage was more uniform for P15‐coated grafts compared to the uncoated controls.     

Novel fluorapatite/niobium composite coating for metallic human body implants

This study's aim was to design and prepare a novel composite coating in order to improve the biocompatibility of the metallic implants. AISI 316L stainless steel (SS) was used as a substrate and a filler-matrix fluorapatite/niobium (FA/Nb) composite coating was performed on the substrate by using plasma-spray technique. XRD and SEM analyses were utilized to characterize the coatings. Electrochemical polarization tests were carried out in two types of physiological solutions in order to evaluate the corrosion behavior of the coated specimens as an indication of biocompatibility. The results indicated that the corrosion current density of the FA/Nb coated samples was much lower than the obtained values for the FA coated SS substrates. Obviously, the novel FA/Nb composite coating could improve the corrosion resistance and the biocompatibility of the SS implants.     

Preparation of modified nano ZnO/polyester/TGIC powder coating nanocomposite and evaluation of its antibacterial activity

Powder coating nanocomposite with antibacterial properties is the aim of this study. For this purpose, nano zinc oxide was modified by vinyltrimethoxysilane (VTMS) and Triethoxy(methyl)silane (TEMS). Then various percentages of modified and non-modified nano ZnO (1, 3 and 5%), polyester resin and triglycidyl isocyanurate as a hardener were blended by twin screw extruder. Prepared polymer–matrix composite (PMC) was atomized and coated by electrostatic method on aluminum plates. Finally, samples were cured for 10 min at 200 °C. For investigating the thermal stabilities of modified nano particles, thermogravimetric analyses (TGA) were used. Antibacterial properties of coatings were investigated by gram negative bacteria Escherichia coli and gram positive Staphylococcus aureus. The results showed that the coatings demonstrate significant antibacterial activity by increasing amounts of ZnO nanoparticles (5%) when were modified by VTMS.