Quantifying the bioadhesive properties of surface-modified polyurethane-urea nanoparticles in the vascular network (original) (raw)
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Biomaterials, 2009
A series of nanocomposites from polyurethane (PU) incorporated with various low concentrations (17.4-174 ppm) of gold nanoparticles (approximately 5 nm) (denoted ''PU-Au'') were used as a model system to study the mechanisms that influenced endothelial cell (EC) migration on biomaterial surfaces. The migration rate of ECs on the PU-Au nanocomposites was determined by a real-time image system. It was found that ECs had the highest migration rate on the nanocomposite containing 43.5 ppm of gold (''PU-Au 43.5 ppm''). The high EC migration rate was associated with increased levels of endothelial nitric oxide synthase (eNOS) and phosphorylated-Akt (p-Akt) expressed by ECs cultured on PU-Au. The inductions of both eNOS and p-Akt on PU-Au were abolished by the addition of LY294002 (PI3K inhibitor), suggesting that these cellular events may be regulated through the PI3K signaling pathway. Using a biotinylated VEGF-165 that recognizes VEGF receptors and by FACS analysis, slightly higher expression of VEGF receptors for ECs on PU-Au was also demonstrated. Phalloidin staining showed that actin appeared as a circumferential band surrounding each cell on tissue culture polystyrene, whereas on PU-Au, especially on PU-Au 43.5 ppm, the cells had their margin spread out and extend processes with stress fibers in the protruding lamellipodia. Moreover, the higher EC migration rate on PU-Au 43.5 ppm was suppressed by LY294002. The higher protein expression of focal adhesion kinase (FAK) on PU-Au 43.5 ppm was observed in FAK-GFP transfected ECs. It was concluded that PU-Au nanocomposites activated FAK and the PI3K/Akt signaling pathway in ECs, leading to proliferation and migration of ECs on these surfaces.
An Insight into the Structural Diversity and Clinical Applicability of Polyurethanes in Biomedicine
Polymers
Due to their mechanical properties, ranging from flexible to hard materials, polyurethanes (PUs) have been widely used in many industrial and biomedical applications. PUs’ characteristics, along with their biocompatibility, make them successful biomaterials for short and medium-duration applications. The morphology of PUs includes two structural phases: hard and soft segments. Their high mechanical resistance featuresare determined by the hard segment, while the elastomeric behaviour is established by the soft segment. The most important biomedical applications of PUs include antibacterial surfaces and catheters, blood oxygenators, dialysis devices, stents, cardiac valves, vascular prostheses, bioadhesives/surgical dressings/pressure-sensitive adhesives, drug delivery systems, tissue engineering scaffolds and electrospinning, nerve generation, pacemaker lead insulation and coatings for breast implants. The diversity of polyurethane properties, due to the ease of bulk and surface mod...
Journal of Materials Science, 2019
Polyurethane (PU) has been utilized in the development of various blood-contacting medical devices owing to their good biocompatibility and mechanical properties. The present study highlights the design and engineering of biomimetic polyurethanes with enhanced hemocompatibility by blending it with polyethylene glycol (PEG) and modifying its surface using gelatin as a surface modifier. The physicochemical characterization of the developed polyurethanes was performed by attenuated total reflectance-Fourier transform infrared spectroscopy, wide-angle X-ray diffraction, water contact angle analysis and water uptake studies, while thermal properties were evaluated using thermogravimetric analysis. The surface protein adsorption pattern along with hemocompatibility of the films was verified by BCA, hemolysis assay, activated partial thromboplastin time, prothrombin time and platelet adhesion studies. Our results demonstrated that the developed polyurethane surfaces modified with PEG and gelatin exhibited increased hydrophilicity which caused enhanced biocompatibility and hemocompatibility. The platelet adhesion was reduced by 92.54% and 88.81% on the developed PU/PEG-4K and PU/PEG-4K/ GEL surfaces, respectively. The in vitro cytocompatibility evaluation was done using HUVECs which confirmed that the developed surfaces were able to promote adhesion and proliferation of HUVECs. The biomimetic polyurethane surfaces co-engineered with PEG and gelatin exhibited excellent hemocompatibility and can be promising candidates for their further evaluation toward their application in the blood-contacting devices.
Surface properties of a specifically modified high-grade medical polyurethane
Surface Science, 2001
A high-grade medical polyurethane (PUR) was speci®cally modi®ed to mimic the vascular vessel lumen. Since vascular endothelium represents a unique non-thrombogenic surface, we developed a surface modi®cation process to design a new PUR surface which promotes endothelial cell adhesion. Biologically active synthetic RGD-containing peptide has been covalently coupled on the PUR surface. In order to optimise the RGD coupling, intermediate steps of PUR surface modi®cation, such as plasma functionalisation and spacer polysaccharide grafting were investigated. Surface topography and friction images, chemistry and wettability dierences of individual modi®cation steps were controlled using atomic and lateral force microscopy, angle-resolved X-ray photoelectron spectroscopy and static contact angle measurements. Human umbilical vein endothelial cells adhesion tests were performed in vitro on all the samples. Only the RGD-containing peptide-grafted PUR has shown the endothelial cell attachment with an almost entire coverage of the surface substrate. Ó
Surface modification and endothelialization of polyurethane for vascular tissue engineering applications: a review, 2017
Cardiovascular implants, especially vascular grafts made of synthetic polymers, find wide clinical applications in the treatment of cardiovascular diseases. However, cases of failure still exist, notably caused by restenosis and thrombus formation. Aiming to solve these problems, various approaches to surface modification of synthetic vascular grafts have been used to improve both the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification using hydrophilic molecules can enhance hemocompatibility, but this may limit the initial vascular endothelial cell adhesion. Therefore, the improvement of endothelialization on these grafts with specific peptides and biomolecules is now an exciting field of research. In this review, several techniques to improve surface modification and endothelialization on vascular grafts, mainly polyurethane (PU) grafts, are summarized, together with the recent development and evolution of the different strategies: from the use of PEG, zwitterions, and polysaccharides to peptides and other biomolecules and genes; from in vitro endothelialization to in vivo endothelialization; and from bio-inert and bio-active to bio-mimetic approaches.
Hemijska industrija, 2014
Segmented polyurethanes based on poly(dimethylsiloxane), currently used for biomedical applications, have sub-optimal biocompatibility which reduces their efficacy. Improving the endothelial cell attachment and blood-contacting properties of PDMS-based copolymers would substantially improve their clinical applications. We have studied the surface properties and in vitro biocompatibility of two series of segmented poly(urethane-dimethylsiloxane)s (SPU-PDMS) based on hydroxypropyl- and hydroxyethoxypropyl- terminated PDMS with potential applications in blood-contacting medical devices. SPU-PDMS copolymers were characterized by contact angle measurements, surface free energy determination (calculated using the van Oss-Chaudhury-Good and Owens-Wendt methods), and atomic force microscopy. The biocompatibility of copolymers was evaluated using an endothelial EA.hy926 cell line by direct contact assay, before and after pre-treatment of copolymers with multicomponent protein mixture, as wel...
2014
The design of new, safe and effective nanotherapeutic systems is an important challenge for the researchers in the nanotechnology area. This study describes the formation of biocompatible polyurethane and polyurea nanoparticles based on polyoxyethylene castor oil derivative surfactant formed from O/W nano-emulsions by polymerization at the droplet interfaces in systems composed by aqueous solution/Kolliphor ® ELP/medium chain triglyceride suitable for intravenous administration. Initial nano-emulsions incorporating highly hydrophilic materials were prepared by the phase inversion composition (PIC) method. After polymerization, nanoparticles with a small particle diameter (25-55 nm) and low polydispersity index were obtained. Parameters such as concentration of monomer, O/S weight ratio as well as the polymerization temperature were crucial to achieve a correct formation of these nanoparticles. Moreover, FT-IR studies showed the full conversion of the monomer to polyurethane and polyurea polymers. Likewise the involvement of the surfactant in the polymerization process through their nucleophilic groups to form the polymeric matrix was demonstrated. This could mean a first step in the development of biocompatible systems formulated with polyoxyethylene castor oil derivative surfactants. In addition, haemolysis and cell viability assays evidenced the good biocompatibility of KELP polyurethane and polyurea nanoparticles thus indicating the potential of these nanosystems as promising drug carriers.
Polyurethane Organosilicate Nanocomposites as Blood Compatible Coatings
Coatings, 2012
Polymer clay nanocomposites (NCs) show remarkable potential in the field of drug delivery due to their enhanced barrier properties. It is hypothesised that well dispersed clay particles within the polymer matrix create a tortuous pathway for diffusing therapeutic molecules, thereby resulting in more sustained release of the drug. As coatings for medical devices, these materials can simultaneously modulate drug release and improve the mechanical performance of an existing polymer system without introducing additional materials with new chemistries that can lead to regulatory concerns. In this study, polyurethane organosilicate nanocomposites (PUNCs) coated onto stainless steel wires were evaluated for their feasibility as blood compatible coatings and as drug delivery systems. Heparin was selected as the model drug to examine the impact of silicate loading and modifier chain length in modulating release. Findings revealed that better dispersion was achieved from samples with lower clay loadings and longer alkyl chains. The blood compatibility of PUNCs as assessed by thrombin generation assays showed that the addition of silicate particles did not significantly decrease the thrombin generation lag time (TGT, p = 0.659) or the peak thrombin (p = 0.999) of polyurethane (PU). PUNC coatings fabricated in this research were not cytotoxic as examined by the cell growth inhibition
iScience
Aortic endothelial cell dysfunction is an early trigger of atherosclerosis, the major cause of the cardiovascular disease (CVD). Nanomedicines targeting vascular endothelium and lesions hold great promise as therapeutic solutions to vascular disorders. This study investigates the vascular delivery efficacy of polyurethanepolyurea nanocapsules (Puua-NCs) with pH-synchronized shell cationization and redox-triggered release. Fluorescent lipophilic dye DiI was encapsulated into Puua-NCs of variable sizes and concentrations. In vitro cellular uptake studies with human aortic endothelial cells showed that these Puua-NCs were taken up by cells in a dose-dependent manner. In apolipoprotein E-deficient mice fed a Western diet, a model of atherosclerosis, circulating Puua-NCs were stable and accumulated in aortic endothelium and lesions within 24 hours after intravenous administration. Treatment with thiol-reducing and oxidizing reagents disrupted the disulfide bonds on the surface of internalized NCs, triggering disassembly and intracellular cargo release. Ultimately, Puua-NCs are a potential redoxcontrollable cardiovascular drug delivery system.
In vitro Interactions of Biomedical Polyurethanes with
2016
ABSTRACT: Three commercial medical-grade polyurethanes (PUs), a poly-ether-urethane (Pellethane), and two poly-carbonate-urethanes, the one aromatic (Bionate) and the other aliphatic (Chronoflex), were tested for macrophages and bacterial cells adhesion, in the presence or absence of adhesive plasma proteins. All the experiments were carried out on PUs films obtained by solvent casting. The wettability of these films was analysed by measuring static contact angles against water. The ability of the selected PUs to adsorb human fibronectin (Fn) and fibrinogen (Fbg) was checked by ELISA with biotin-labelled proteins. All PUs were able to adsorb Fn and Fbg (Fn>Fbg). Fn adsorption was in the order: Pellethane>Chronoflex>Bionate, the highest Fbg adsorption being detected onto Bionate (Bionate>Chronoflex>Pellethane). The human macrophagic line J111, and the two main bacterial strains responsible for infection in humans (Staphylococcus aureus Newman and Staphylococcus epiderm...