Implementación, caracterización y validación biológica de técnicas de modificación superficial de titanio poroso pulvimetalúrgico para aplicaciones biomédicas.

El titanio comercialmente puro es bien conocido como un material metálico que presenta un comportamiento in vivo adecuado, siendo reconocido como un buen candidato en los reemplazos del tejido óseo cortical. Sin embargo, el fenómeno de apantallamiento de tensiones y la deficiente osteointegración son aún limitaciones por resolver. En este contexto, se fabricaron sustratos de titanio poroso mediante la técnica de espaciadores (50 vol% de NH4HCO3, con dos rangos distintos de tamaño de partícula: 100-200 and 250-355 μm). Las muestras se prensaron a 800 MPa y se sinterizaron a 1250 ºC durante 2h, obteniendo un equilibrio entre la resistencia mecánica y la rigidez y reduciendo el módulo de Young de las muestras. Para mejorar el crecimiento e infiltración del hueso, así como la osteointegración, se implementaron diferentes técnicas de modificación superficial. Estos métodos pueden clasificarse en tres tipos. Uno de ellos consistió en generar rugosidad en la superficie plana y en el interior de los poros mediante ataque químico (inmersión de los sustratos en una solución de HF a 125 y 625 s). La rugosidad adicional sobre la topografía potenció la adhesión de osteoblastos, mejorando así la oseointegración. El segundo método está relacionado con transformar la superficie de los sustratos en bioactiva, mediante la deposición de recubrimientos bioactivos. Para este propósito, se depositaron hidroxiapatita (HA) y vidrio bioactivo (BG) sobre los sustratos, usando la técnica de sol-gel y la sedimentación por goteo, respectivamente. Adicionalmente, los sustratos recubiertos con vidrio bioactivo se sumergieron en fluido corporal simulado (SBF) para evaluar la precipitación de HA. Los recubrimientos bioactivos cubrieron y penetraron en los poros, consiguiendo una mejor adhesión entre el titanio y el hueso. Finalmente, el último proceso se basa en el uso de un recubrimiento de SPEEK, depositado sobre los sustratos de titanio. El éxito de este método se evaluó en términos del comportamiento antibacteriano. En concreto, una cepa bacteriana de MRSA fue cultivada. La presencia del recubrimiento de SPEEK inhibió la adhesión y proliferación de bacterias, evitando posibles infecciones alrededor del implante de titanio. Todos los sustratos, porosos y densos, fueron caracterizados antes y después de cada modificación superficial. La caracterización se llevó a cabo en términos de micro-estructura (densidad, porosidad, composición y fases), topografía (superficie y área de rugosidad), comportamiento mecánico macro (Ed, Ec, σy) y micro-mecánico (micro-dureza Vickers, curvas P-h), y comportamiento tribológico (resistencia al rayado y al desgaste). Además, la oseointegración se estudió mediante el cultivo celular (premioblastos C2C12-GFP) y bacteriano (cepas E. coli, P. aeruginosa y MRSA), en términos de su adhesión y proliferación. En resumen, se concluyó que los sustratos recubiertos con HA, BG y SPEEK presentan buenas propiedades biomecánicas (rigidez y límite elástico), debido a que la porosidad del sustrato no se altera. Sin embargo, los sustratos atacados mostraron una degradación importante en el comportamiento mecánico. Además, todos los tratamientos superficiales, consiguieron un sistema biofuncional, promoviendo el crecimiento del hueso hacia el interior y mejorando la oseointegración. Por tanto, pueden ser considerados como solución en los reemplazos óseos totales y/o parciales

Designing bioactive porous titanium interfaces to balance mechanical properties and in vitro cells behavior towards increased osseointegration

Titanium implant failures are mainly related to stress shielding phenomenon and the poor cell interaction with host bone tissue. The development of bioactive and biomimetic Ti scaffolds for bone regeneration remains a challenge which needs the design of Ti implants with enhanced osseointegration. In this context, 4 types of titanium samples were fabricated using conventional powder metallurgy, fully dense, dense etched, porous Ti, and porous etched Ti. Porous samples were manufactured by space holder technique, using ammonium bicarbonate particles as spacer in three different ranges of particle size (100–200 μm, 250–355 μm and 355–500 μm). Substrates were chemically etched by immersion in fluorhydric acid at different times (125 and 625 s) and subsequently, were characterized from a micro-structural, topographical and mechanical point of view. Etched surfaces showed an additional roughness preferentially located inside pores. In vitro tests showed that all substrates were biocompatible (80% of cell viability), confirming cell adhesion of premioblastic cells. Similarly, osteoblast showed similar cell proliferation rates at 4 days, however, higher cell metabolic activity was observed in fully dense and dense etched surfaces at 7 days. In contrast, a significant increase of alkaline phosphatase enzyme expression was observed in porous and porous etched samples compared to control surfaces (dense and dense etched), noticing the suitable surface modification parameters (porosity and roughness) to improve cell differentiation. Furthermore, the presence of pores and rough surfaces of porous Ti substrates remarkably decreased macrophage activation reducing the M1 phenotype polarization as well M1 cell marker expression. Thus, a successful surface modification of porous Ti scaffolds has been performed towards a reduction on stress shielding phenomenon and enhancement of bone osseointegration, achieving a biomechanical and biofunctional equilibrium.Ministry of Economy and Competitiveness of Spain grant MAT2015-71284-PJunta de Andalucía – FEDER (Spain) Project Ref. P12-TEP-140

Porous Titanium surfaces to control bacteria growth: mechanical properties and sulfonated polyetheretherketone coating as antibiofounling approaches

Here, titanium porous substrates were fabricated by a space holder technique. The relationship between microstructural characteristics (pore equivalent diameter, mean free-path between pores, roughness and contact surface), mechanical properties (Young’s modulus, yield strength and dynamic micro-hardness) and bacterial behavior are discussed. The bacterial strains evaluated are often found on dental implants: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. The colony-forming units increased with the size of the spacer for both types of studied strains. An antibiofouling synthetic coating based on a sulfonated polyetheretherketone polymer revealed an effective chemical surface modification for inhibiting MRSA adhesion and growth. These findings collectively suggest that porous titanium implants designed with a pore size of 100–200 µm can be considered most suitable, assuring the best biomechanical and bifunctional anti-bacterial properties.University of Seville VI Plan Propio de Investigación y Transferencia—US 2018, I.3A

Balancing porosity and mechanical properties of titanium samples to favor cellular growth against bacteria

Two main problems limit the success of titanium implants: bacterial infection, which restricts their osseointegration capacity; and the stiffness mismatch between the implant and the host cortical bone, which promotes bone resorption and risk of fracture. Porosity incorporation may reduce this difference in stiffness but compromise biomechanical behavior. In this work, the relationship between the microstructure (content, size, and shape of pores) and the antibacterial and cellular behavior of samples fabricated by the space-holder technique (50 vol % NH4HCO3 and three ranges of particle sizes) is established. Results are discussed in terms of the best biomechanical properties and biofunctional activity balance (cell biocompatibility and antibacterial behavior). All substrates achieved suitable cell biocompatibility of premioblast and osteoblast in adhesion and proliferation processes. It is worth to highlighting that samples fabricated with the 100–200 μm space-holder present better mechanical behavior—in terms of stiffness, microhardness, and yield strength—which make them a very suitable material to replace cortical bone tissues. Those results exposed the relationship between the surface properties and the race of bacteria and mammalian cells for the surface with the aim to promote cellular growth over bacteria.University of Seville (Spain) VI Plan Propio de Investigación y Transferencia—US 2018, I.3A

Bioactive Coatings on Porous Titanium for Biomedical Applications

Commercial pure titanium is a recognized and accepted material for cortical bone tissue substitution. However, stress-shielding phenomena and lack of osseointegration result in significant limitations. This work is focused on the achievement of an effective solution for both problems via fabrication of porous titanium substrates coated with bioactive glass. Substrates were obtained through the space holder technique giving values of stiffness and yield strength compatible with cortical bone tissue to reduce the stress-shielding phenomenon. Titanium substrates were coated with different number of layers of bioactive glass 45S5 by dripping sedimentation. The substrates porosity was characterized by different techniques. Ultrasound, compression and micro-mechanical testing were used for mechanical properties evaluation. After substrates coating, the infiltration ability, coating homogeneity and structural integrity (chipping and cracking) were evaluated for each coating layer. The chemical composition of coating and phases were studied before and after in vitro tests in Simulated Body Fluid. The results showed more homogenous coating, adherence and greater hydroxyapatite growth for the tri-layer system in both dense and porous samples. Besides, the relation of Ca/P was closed to that of stoichiometric hydroxyapatite in the human body. The coated porous titanium could be potentially used in load bearing partial implants with improved osseointegration.Ministry of Economy and Competitiveness of the State General Administration of Spain grant MAT2015-71284-

Bacterial behavior on coated porous titanium substrates for biomedical applications

In this work, bacterial behavior on dense and porous titanium substrates is discussed. Porous titanium was fabricated by a space holder technique (using 50 vol%, NH4HCO3 with particle sizes between 250 and 355 μm). These substrates were coated by sulfonated PEEK (termed SPEEK). Characterization of the porous substrate was carried out using the Archimedes Method, Image Analysis, and three-dimensional X-ray Micro-Computed Tomography (including total and interconnected porosity, equivalent diameter, and pore shape factor), as well as mechanical characterization (specifically stiffness and yield strength). A detailed study was performed here to investigate the influence of substrate porosity on the adhesion and proliferation of E. coli, MRSA, and P. aeruginosa (common causes of orthopedic device-associated infections). Bacterial colonization was examined in terms of the initial bacterial concentration, as well as bacterial adherence to and growth on the surface and inside the pores. Results suggest that fully dense titanium supported the least bacterial colonization, while the porous titanium promoted bacterial growth in the medium and inside the cavities. Furthermore, the SPEEK coating deposited onto the samples inhibited bacteria growth inside the porous materials. In this manner, this study showed for the first time that SPEEK could have potential antibacterial properties to offset the increase in bacteria growth commonly observed in porous materials.Junta de Andalucía-FEDER (Spain) Ref. P12-TEP-1401Ministry of Economy and Competitiveness of Spain, MAT2015-71284-

Sol-gel deposition of hydroxyapatite coatings on porous titanium for biomedical applications

The stress shielding and the poor osseointegration in titanium implants are still problems to be resolved. In this context, this work proposes a balanced solution. Titanium samples were fabricated, with a porosity of 100-200 µm of pore size employing space-holder technique (50 vol. % NH4HCO3, 800 MPa at 1250 ºC during 2h under high vacuum conditions), obtaining a good equilibrium between stiffness and mechanical resistance. The porous titanium substrates were coated with hydroxyapatite, obtained by sol-gel technique: immersion, dried at 80ºC and heat treatment at 450ºC during 5h under vacuum conditions. Phases, surface morphology and interfacial microstructure of the transverse section were analyzed by Micro-Computed Tomography, SEM and confocal laser, as well as the infiltration capability of the coating into the metallic substrate pores. The FTIR and XRD showed the crystallinity of the phases and the chemical composition homogeneity of the coating. The size and interconnected pores obtained allow the infiltration of hydroxyapatite (HA), possible bone ingrowth and osseointegration. The scratch resistance of the coating corroborated a good adherence to the porous metallic substrate. The coated titanium samples have a biomechanical and biofunctional equilibrium, as well as a potential use in biomedical applications (partial substitution of bone tissue).Junta de Andalucía-FEDER (Spain) Project Ref. P12-TEP-1401Spanish Ministry of Economy and Competitiveness Grant No. MAT2015-71284-

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Virgen del Rocío Hospital COVID-19 Working Team José Miguel Cisneros, Sonsoles Salto-Alejandre, Judith Berastegui-Cabrera, Pedro Camacho-Martínez, Carmen Infante-Domínguez, Marta Carretero-Ledesma, Juan Carlos Crespo-Rivas, Eduardo Márquez, José Manuel Lomas, Claudio Bueno, Rosario Amaya, José Antonio Lepe, Jerónimo Pachón, Elisa Cordero, Javier Sánchez-Céspedes, Manuela Aguilar-Guisado, Almudena Aguilera, Clara Aguilera, Teresa Aldabo-Pallas, Verónica Alfaro-Lara, Cristina Amodeo, Javier Ampuero, María Dolores Avilés, Maribel Asensio, Bosco Barón-Franco, Lydia Barrera-Pulido, Rafael Bellido-Alba, Máximo Bernabeu-Wittel, Candela Caballero-Eraso, Macarena Cabrera, Enrique Calderón, Jesús Carbajal-Guerrero, Manuela Cid-Cumplido, Yael Corcia-Palomo, Juan Delgado, Antonio Domínguez-Petit, Alejandro Deniz, Reginal Dusseck-Brutus, Ana Escoresca-Ortega, Fátima Espinosa, Nuria Espinosa, Michelle Espinoza, Carmen Ferrándiz-Millón, Marta Ferrer, Teresa Ferrer, Ignacio Gallego-Texeira, Rosa Gámez-Mancera, Emilio García, Horacio García-Delgado, Manuel García-Gutiérrez, María Luisa Gascón-Castillo, Aurora González-Estrada, Demetrio González, Carmen Gómez-González, Rocío González-León, Carmen Grande-Cabrerizo, Sonia Gutiérrez, Carlos Hernández-Quiles, Inmaculada Concepción Herrera-Melero, Marta Herrero-Romero, Luis Jara, Carlos Jiménez-Juan, Silvia Jiménez-Jorge, Mercedes Jiménez-Sánchez, Julia Lanseros-Tenllado, Carmina López, Isabel López, Álvaro López-Barrios, Luis F. López-Cortés, Rafael Luque-Márquez, Daniel Macías-García, Guillermo Martín-Gutiérrez, Luis Martín-Villén, José Molina, Aurora Morillo, María Dolores Navarro-Amuedo, Dolores Nieto-Martín, Francisco Ortega, María Paniagua-García, Amelia Peña-Rodríguez, Esther Pérez, Manuel Poyato, Julia Praena-Segovia, Rafaela Ríos, Cristina Roca-Oporto, Jesús F. Rodríguez, María Jesús Rodríguez-Hernández, Santiago Rodríguez-Suárez, Ángel Rodríguez-Villodres, Nieves Romero-Rodríguez, Ricardo Ruiz, Zida Ruiz de Azua, Celia Salamanca, Sonia Sánchez, Víctor Manuel Sánchez-Montagut, César Sotomayor, Alejandro Suárez Benjumea & Javier ToralSevere Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19.This work was supported by Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades Junta de Andalucia (research Project CV20-85418), Consejeria de salud Junta de Andalucia (Research Contract RH-0037-2020 to JV) the Instituto de Salud Carlos III (CP19/00159 to AGV, FI17/00186 to MRJL, FI19/00083 to MCGC, CM20/00243 to APG, and COV20/00698 to support COHVID-GS) and the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020 and RD16/0025/0026), which is included in the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, 2008 to 2011 and 2013 to 2016, Instituto de Salud Carlos III, Fondos FEDER. ERM was supported by the Spanish Research Council (CSIC).Peer reviewe

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio