Development of Multifunctional Materials Based on Poly(ether ether ketone) with Improved Biological Performances for Dental Applications.

The main target for the future of materials in dentistry aims to develop dental implants that will have optimal integration with the surrounding tissues, while preventing or avoiding bacterial infections. In this project, poly(ether ether ketone) (PEEK), known for its suitable biocompa-tibility and mechanical properties for dental applications, was loaded with 1, 3, and 5 wt.% ZnO nanoparticles to provide antibacterial properties and improve interaction with cells. Sample cha-racterization by X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) as well as mechanical properties showed the presence of the nanoparticles and their effect in PEEK matrices, preserving their relevant properties for dental applications. Al-though, the incorporation of ZnO nanoparticles did not improve the mechanical properties and a slight decrease in the thermal stability of the materials was observed. Hemocompatibility and osteoblasts-like cell viability tests showed improved biological performances when ZnO was present, demonstrating high potential for dental implant applications.

Surface modification and direct plasma amination of L605 CoCr alloys: on the optimization of the oxide layer for application in cardiovascular implants.

Stents are cardiovascular devices used to treat atherosclerosis, and are deployed into narrowed arteries and implanted by expansion to reopen the biological lumen. Nevertheless, complications after implantation are still observed in 10-14% of the implantations. Therefore, functionalizing these devices with active molecules to improve the interfacial effects with the surrounding tissue strongly impacts their success. A plasma-based procedure to directly graft biomolecules to the surface of cobalt chromium alloys, without any polymeric coating, has been recently reported. Assuring the stability of the coating during plastic deformation generated during the implantation whilst avoiding the corrosion of the surface is crucial. This study explores different surface treatments to be used as a pre-treatment for this novel procedure. The effects of (i) electropolishing, (ii) thermal treatments, and (iii) the plasma immersion ion implantation of oxygen on the chemical composition, roughness, wettability and efficiency during the plasma-amination procedure whilst avoiding cracks after deformation, thus maintaining corrosion resistant behaviour, were investigated by XPS, AFM, ToF-SIMS imaging and depth profile, and WCA. Furthermore, the hemocompatibility of the surface and cell viability assays were also performed. Results showed that all of the treatments created a different surface chemical composition: EP mainly of chromium oxide, PIII with a layer of cobalt oxide and TT with a mixture of oxides, as observed by XPS and ToF-SIMS. Moreover, EP was the process that generated a surface with the highest efficiency to amination and the most corrosion resistance among the treatments, and it appeared as the most suitable pre-treatment for stent functionalization.

A comparison of adsorbed and grafted fibronectin coatings under static and dynamic conditions.

Coatings for medical devices are expected to improve their surface biocompatibility mainly by being bioactive, i.e. stimulating healing-oriented interactions with living cells, tissues and organs. In particular, for stent applications, coatings are often designed to enhance the endothelialization process. The coating strategy will be primarily responsible for the interfacial properties between the substrate and the coating, which must show high stability. Therefore, the present work aims at comparing the stability of adsorbed and grafted fibronectin, a protein well-known to promote endothelialization. Fibronectin coatings were deposited on fluorocarbon films generated by a plasma-based process on stainless steel substrates. Then, deformation tests were performed in order to simulate the stenting procedure and stability tests were completed under static and under-flow conditions. Coatings were characterized by XPS, AFM, water contact angle, immunostaining and ToF-SIMS analyses. The results show higher stability for the grafted coatings; indeed, the integrity of the protein simply adsorbed was strongly compromised especially after under-flow tests. Both coatings exhibited similar behavior after deformation and static tests. These results clearly show the impact of the coating strategy on the overall stability of the coatings as well as the importance of under-flow investigations.

Fibronectin adsorption on surface-modified polyetherurethanes and their differentiated effect on specific blood elements related to inflammatory and clotting processes.

After the introduction of a medical device into the body, adhesive proteins such as fibronectin (Fn) will adsorb to the surface of the biomaterial. Monocytes (MCs) will interact with these adsorbed proteins, and adopt either a proinflammatory and/or prowound healing phenotype, thereby influencing many blood interaction events including thrombogenesis. In this work, Fn adsorption as well as subsequent MC response and thrombus formation were investigated on two surfaces-modified polyetherurethanes (PEUs) using different surface modifiers: an anionic/dihydroxyl oligomeric (ADO) additive, known to enable cell adhesion, and a fluorinated polypropylene oxide oligomer (PPO), known to reduce platelet adhesion. Results indicated that at 24 h of MC culture, PEU-ADO and PEU-PPO promoted an anti-inflammatory character relative to the base PEU. Longer clotting times, based on a free hemoglobin assay, were also found on the two surface-modified PEUs relative to the native one, suggesting their potential for the reduction of thrombus formation. In presence of a Fn monolayer, the surface-modified PEUs conserved a lower thrombogenic character than the base PEU, and was however significantly decreased when compared to prior protein adsorption. Furthermore, Fn coatings increased the MC production levels of tumor necrosis factor-α and interleukin-10 at 24 h, while not affecting the anti-inflammatory effect of the modifications relative to the base PEU. This finding was most prominent on PEU-PPO, suggesting that the interaction of the adsorbed Fn with blood cells was different for the two additives. Hence, the results highlighted differentiating effects of Fn adsorption on specific blood activating processes related to inflammatory and thrombotic responses.

On the potential for fibronectin/phosphorylcholine coatings on PTFE substrates to jointly modulate endothelial cell adhesion and hemocompatibility properties.

The use of biomolecules as coatings on biomaterials is recognized to constitute a promising approach to modulate the biological response of the host. In this work, we propose a coating composed by 2 biomolecules susceptible to provide complementary properties for cardiovascular applications: fibronectin (FN) to enhance endothelialization, and phosphorylcholine (PRC) for its non thrombogenic properties. Polytetrafluoroethylene (PTFE) was selected as model substrate mainly because it is largely used in cardiovascular applications. Two approaches were investigated: 1) a sequential adsorption of the 2 biomolecules and 2) an adsorption of the protein followed by the grafting of phosphorylcholine via chemical activation. All coatings were characterized by immunofluorescence staining, X-Ray Photoelectron Spectroscopy and Scanning Electron Microscopy analyses. Assays with endothelial cells showed improvement on cell adhesion, spreading and metabolic activity on FN-PRC coatings compared with the uncoated PTFE. Platelets adhesion and activation were both reduced on the coated surfaces when compared with uncoated PTFE. Moreover, clotting time tests exhibited better hemocompatibility properties of the surfaces after a sequential adsorption of FN and PRC. In conclusion, FN-PRC coating improves cell adhesion and non-thrombogenic properties, thus revealing a certain potential for the development of this combined deposition strategy in cardiovascular applications.

Dextran grafting on PTFE surface for cardiovascular applications.

The modification of biomaterial surfaces with biomolecules influences the biological response. In this work, caboxymethyldextrans (CMD) with different degrees of substitution have been grafted to surfaces by introduction of amino moieties directly onto the substrate surface. Polytetrafluoroethylene was selected as a model substrate for biomaterial as it is already largely used for cardiovascular clinical applications. Firstly, CMD polymers were characterized by FTIR, (1)H-NMR, and conductimetric titration. Then, the coatings have been analyzed by XPS to confirm the grafting and determine the composition. Once characterized, biological performances of CMD coatings were investigated. The hemocompatibility was ascertained using the free hemoglobin method. The effects on endothelial and smooth muscle cell adhesion were also studied. Results indicated that CMD at a 0.2 substitution degree, significantly influenced the biological property of PTFE by exhibiting non-thrombogenic properties as well as enhancing endothelial cell adhesion along with limiting smooth muscle cell adhesion. This work suggested the creation of versatile pro-active biomaterials suitable for different biomedical applications.