Dual-action effect of gallium and silver providing osseointegration and antibacterial properties to calcium titanate coatings on porous titanium implants

Previously, functional coatings on 3D-printed titanium implants were developed to improve their biointegration by separately incorporating Ga and Ag on the biomaterial surface. Now, a thermochemical treatment modification is proposed to study the effect of their simultaneous incorporation. Different concentrations of AgNO3 and Ga(NO3)3 are evaluated, and the obtained surfaces are completely characterized. Ion release, cytotoxicity, and bioactivity studies complement the characterization. The provided antibacterial effect of the surfaces is analyzed, and cell response is assessed by the study of SaOS-2 cell adhesion, proliferation, and differentiation. The Ti surface doping is confirmed by the formation of Ga-containing Ca titanates and nanoparticles of metallic Ag within the titanate coating. The surfaces generated with all combinations of AgNO3 and Ga(NO3)3 concentrations show bioactivity. The bacterial assay confirms a strong bactericidal impact achieved by the effect of both Ga and Ag present on the surface, especially for Pseudomonas aeruginosa, one of the main pathogens involved in orthopedic implant failures. SaOS-2 cells adhere and proliferate on the Ga/Ag-doped Ti surfaces, and the presence of gallium favors cell differentiation. The dual effect of both metallic agents doping the titanium surface provides bioactivity while protecting the biomaterial from the most frequent pathogens in implantology.Peer ReviewedPostprint (published version

Mecanismos moleculares implicados en el daño vascular y renal causado por la angiotensina II: modulación terapéutica

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 23 de Junio de 200

Bactericidal silver-doped DLC coatings obtained by pulsed filtered cathodic arc co-deposition

Diamond-like carbon (DLC) coatings have been extensively studied over the last two decades in the field of materials engineering. The addition of effective bactericidal agents like silver suggests the potential application of silver-doped DLC coatings in the biomedical sector. In this paper, DLC coatings containing about 2 at. % Ag were grown on CoCrMo substrates by pulsed filtered cathodic arc co-deposition using pure graphite and silver targets. Morphology, structure and chemical composition of the coatings were characterized by SEM, XPS, XRD, Raman and HRTEM. Wettability and surface free energy were also measured. Mechanical properties were analyzed by means of nanoindentation and Rockwell-C adhesion tests. Corrosion resistance of coated and uncoated samples was determined by potentio-dynamic polarization tests in Hank's solution. Cytotoxicity and antibacterial activity against S. aureus and P. aeruginosa were also studied. For comparative purposes, nitrogen-doped DLC coatings obtained by RF magnetron sputtering were also prepared and characterized. Well-adhered and corrosion resistant Ag-DLC nanostructured coatings of up to 1.5 µm thick and 21 GPa in hardness were obtained. The doping concentration of silver studied in this work seems to be optimal for the preparation of non-cytotoxic coatings with a significant bactericidal activity.This work has been financed by the Ministry of the Economy, Industry and Competitiveness of Spain under the project BIOPLASMA (MAT2015-67103-C4).Peer ReviewedPreprin

The Rho-kinase pathway regulates angiotensin II-induced renal damage

The Rho-kinase pathway regulates angiotensin II-induced renal damageBackgroundAngiotensin II (AngII) is a key factor in the pathogenesis of renal damage. AngII via AngII type 1 receptors activates several intracellular signaling systems, including the small guanosine triphosphatase Rho and its downstream effector Rho-dependent serine-threonine kinase (Rho-kinase). The Rho/Rho-kinase pathway contributes to inflammatory and proliferative changes observed in cardiovascular diseases. However, the data on renal diseases are scarce. The aim of this study was to investigate the effect of Rho-kinase inhibition in AngII-induced renal damage.MethodsWe used the model of systemic AngII infusion into normal rats (100 ng/kg per minute; subcutaneous osmotic minipumps), and some animals were treated with the Rho-kinase inhibitor Y-27632 (30 mg/kg per day). In the kidneys of these animals, we evaluated renal lesions, transcription factor activity (by electrophoretic mobility shift assay), and messenger RNA (by polymerase chain reaction) and protein expression levels (by Western blot and/or immunohistochemistry) of proinflammatory and profibrotic factors.ResultsRats infused with AngII for three days present renal inflammatory cell infiltration and slight tubular damage, which were diminished by treatment with the Rho-kinase inhibitor Y-27632. AngII activates nuclear factor-κB and causes overexpression of proinflammatory factors, including cytokines (tumor necrosis factor α) and chemokines (monocyte chemotactic protein-1), and of profibrotic factors (connective tissue growth factor). Treatment of AngII-infused rats with Y-27632 decreases the upregulation of these proinflammatory and profibrotic mediators.ConclusionThese data demonstrate that the Rho-kinase pathway is involved in renal damage caused by AngII through the regulation of proinflammatory and profibrotic mediators. These results suggest that inhibition of the Rho-kinase pathway represents a novel therapy for renal diseases associated with local AngII generation