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While titanium dental implants have already been clinically established, ongoing research is continuously being conducted to advance the fields of osseointegration and bacterial resistance, seeking further improvements in these areas. In this study, we introduce an innovative method for treating titanium surfaces within tightly sealed packaging. Specifically, titanium discs, enclosed in surgical-grade packaging, underwent treatment using cold atmospheric plasma (CAP). The surfaces were thoroughly characterized in terms of wettability, crystalline structure, and chemical composition. Hemocompatibility analyses were conducted using blood diluted in sodium citrate (1:9) exposed to titanium discs for 30 min inside a CO2 incubator at 37 °C. Subsequently, various blood parameters were evaluated, including prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet adhesion. Microbiological analyses were also performed using Pseudomonas aeruginosa (ATCC 27853) for 4 h at 37 °C. The treatment with CAP Jet resulted in a reduction in contact angle without causing any changes in the crystalline structure. No statistically significant differences were observed in the blood parameters. The plasma-treated samples exhibited lower PT and APTT values compared to those of the control group. The surfaces treated with CAP Jet showed increased platelet activation, platelet density, and thrombus formation when compared with the untreated samples. Moreover, the treated surfaces demonstrated lower bacterial colony formation compared with other surfaces.

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INTRODUCTION: Thrombotic disorders are among the leading causes of morbidity and mortality worldwide. Drugs used in the prevention and treatment of atherothrombosis have pharmacokinetic limitations and adverse effects such as hemorrhagic conditions, highlighting the importance of developing more effective antiplatelet agents. ethod: In this work, we synthesized N,N'-disubstituted ureas 3a-3j and evaluated their antiplatelet profiles through in vitro, ex vivo, and in silico studies. The synthesized derivatives exhibited a selective inhibitory profile against platelet aggregation induced by arachidonic acid (AA) in vitro, without significantly affecting other aspects of primary hemostasis and blood coagulation. The compounds that showed inhibition greater than 85% were submitted to the analysis of their potency by calculating the concentration required to inhibit 50% of platelet aggregation induced by AA (IC50). Urea derivative 3a was the most potent with IC50 of 1.45 µM. Interestingly, this derivative inhibited more than 90% of platelet aggregation induced by AA ex vivo, with a similar effect to acetylsalicylic acid. In the hemolysis assay, most of the urea derivatives presented values below 10% suggesting good hemocompatibility. Additionally, the compounds tested at 100 µM also showed no cytotoxic effects in HepG2 and Vero cells. RESULT: The in silico results suggested that compound 3a may bind to the key residue of COX-1 similar to AA and known COX-1 inhibitors, and the results are also in agreement with our SAR, which suggests that the inhibition of this enzyme is the most likely mechanism of antiplatelet activity. CONCLUSION: Therefore, these results demonstrated that N,N'-disubstituted ureas are promising candidates for the development of novel antiplatelet agents.

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BACKGROUND: The reactivity of blood with non-endothelial surface is a challenge for long-term Ventricular Assist Devices development, usually made with pure titanium, which despite of being inert, low density and high mechanical resistance it does not avoid the thrombogenic responses. Here we tested a modification on the titanium surface with Laser Induced Periodic Surface Structures followed by Diamond Like Carbon (DLC) coating in different thicknesses to customize the wettability profile by changing the surface energy of the titanium. METHODS: Four different surfaces were proposed: (1) Pure Titanium as Reference Material (RM), (2) Textured as Test Sample (TS), (3) Textured with DLC 0.3µm as (TSA) and (4) Textured with 2.4µm DLC as (TSB). A single implant was positioned in the abdominal aorta of Wistar rats and the effects of hemodynamic interaction were evaluated without anticoagulant drugs. RESULTS: After twelve weeks, the implants were extracted and subjected to qualitative analysis by Scanning Electron Microscopy under low vacuum and X-ray Energy Dispersion. The regions that remained in contact with the wall of the aorta showed encapsulation of the endothelial tissue. TSB implants, although superhydrophilic, have proven that the DLC coating inhibits the adhesion of biological material, prevents abrasive wear and delamination, as observed in the TS and TSA implants. Pseudo- neointimal layers were heterogeneously identified in higher concentration on Test Surfaces.

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Cardiovascular stenting is the most widely used therapy to treat coronary artery disease caused by partial or total obstruction of the artery due to atherosclerotic plaque formation, with potentially fatal effects. There are different types of stents: bare metal stents, drug-eluting stents, bioabsorbable stents and dual therapy stents. However, they can lead to long-term complications, such as in-stent restenosis and late thrombosis. To reduce these adverse effects, research has focused on biodegradable metallic stents, since they retain the mechanical properties necessary to contain the injured artery while it is being repaired and, once their function has been fulfilled, the stent degrades without altering the system or compromising the patient's health. In this work we have evaluated the biological response of the degradation products of a bare Mg based biomaterial surface-modified by the plasma electrolytic oxidation (PEO) method on vascular tissue cells, hemocompatibility and inflammatory response. The results obtained are compatible with a biosafe material for future use as a cardiovascular implant, but it is necessary to continue with in vivo and mechanical properties tests to ensure and guarantee its use. SIGNIFICANCE STATEMENT: The development of fully bioresorbable stents is a promising alternative for the management of coronary artery disease without causing long-term problems at the implantation site. In this work, the hematological and immunological biocompatibility of bare Mg modified superficially by plasma electrolytic oxidation (PEO-Mg) was evaluated by in vitro and ex vivo assays. PEO-Mg was found to be compatible with blood and immune components surrounding the implantation site with no signs of toxicity to endothelial cells, macrophages, and arterial tissue. In addition, degradation products of PEO-Mg are eliminated by phagocytosis. However, an in-depth study of the physical and mechanical properties and in vivo biocompatibility must be carried out for its future use as a biomedical implant.

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The increased demand for vascular grafts for the treatment of cardiovascular diseases has led to the search for novel biomaterials that can achieve the properties of the tissue. According to this, the investigation of polyurethanes has been a promising approach to overcome the present limitations. However, some biological properties remain to be overcome, such as thrombogenicity and hemocompatibility, among others. This paper aims to synthesize polyurethanes based on castor oil and castor oil transesterified with triethanolamine (TEA) and pentaerythritol (PE) and with the incorporation of 1% chitosan. Analysis of the wettability, enzymatic degradation, mechanical properties (tensile strength and elongation at break), and thermal stability was performed. Along with the evaluation of the cytotoxicity against mouse fibroblast (L929) and human dermal fibroblast (HDFa) cells, the hemolysis rate and platelet adhesion were determined. The castor-oil-based polyurethanes with and without 1% chitosan posed hydrophobic surfaces and water absorptions of less than 2% and enzymatic degradation below 0.5%. Also, they were thermally stable until 300 °C, with tensile strength like cardiovascular tissues. The synthesized castor oil/chitosan polyurethanes are non-cytotoxic (cell viabilities above 80%) to L929 and HDFa cells and non-thrombogenic and non-hemolytic (less than 2%); therefore, they are suitable for cardiovascular applications.

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Tissue engineering has focused on the development of biomaterials that emulate the native extracellular matrix. Therefore, the purpose of this research was oriented to the development of nanofibrillar bilayer membranes composed of polycaprolactone with low and medium molecular weight chitosan, evaluating their physicochemical and biological properties. Two-bilayer membranes were developed by an electrospinning technique considering the effect of chitosan molecular weight and parameter changes in the technique. Subsequently, the membranes were evaluated by scanning electron microscopy, Fourier transform spectroscopy, stress tests, permeability, contact angle, hemolysis evaluation, and an MTT test. From the results, it was found that changes in the electrospinning parameters and the molecular weight of chitosan influence the formation, fiber orientation, and nanoarchitecture of the membranes. Likewise, it was evidenced that a higher molecular weight of chitosan in the bilayer membranes increases the stiffness and favors polar anchor points. This increased Young's modulus, wettability, and permeability, which, in turn, influenced the reduction in the percentage of cell viability and hemolysis. It is concluded that the development of biomimetic bilayer nanofibrillar membranes modulate the physicochemical properties and improve the hemolytic behavior so they can be used as a hemocompatible biomaterial.

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In the present study, the modification of branched polyethyleneimine (b-PEI) was carried out using mesquite gum (MG) to improve its hemocompatibility to be used in biomedical applications. In the copolymer synthesis process (carboxymethylated mesquite gum grafted polyethyleneimine copolymer (CBX-MG-PEI), an MG carboxymethylation reaction was initially carried out (carboxymethylated mesquite gum (CBX-MG). Subsequently, the functionalization between CBX-MG and b-PEI was carried out using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as crosslinking agents. The synthesis products were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). Thermogravimetric analysis showed that CBX-MG and CBX-MG-PEI presented a lower decomposition temperature than MG. The CBX-MG-PEI has a high buffer capacity in the pH range of 4 to 7, similar to the b-PEI. In addition, the CBX-MG-PEI showed an improvement in hemocompatibility in comparison with the b-PEI. The results showed a non-hemolytic property at doses lower than 0.1 µg/mL (CBX-MG-PEI). These results allow us to propose that this copolymer be used in transfection, polymeric nanoparticles, and biomaterials due to its physicochemical and hemocompatibility properties.

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In the present work, gold nanoparticles were synthesized through a green route by using, for the first time, polysaccharides extracted from pineapple gum (PG) as the reducing and capping agent. The obtained nanoparticles (AuNPs-PG) were characterized by UV-VIS, FTIR, TEM, FESEM, EDX, XRD, and zeta potential measurements, which confirmed that PG was effective to produce AuNPs with an average diameter of 10.3 ± 1.6 nm. The AuNPs-PG were employed as the modifier of glassy carbon paste electrodes (CPE/AuNPs-PG), which were applied as sensitive electrochemical sensors to the determination of the antihistamine drug promethazine hydrochloride (PMZ). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements showed that the AuNPs-PG could enhance the electronic transfer properties of the glassy carbon paste, which was due to their large surface area and high electrical conductivity. After optimization of the instrumental parameters of square wave voltammetry (SWV) through a Box-Behnken factorial design, a linear relationship between the anodic peak current and PMZ concentration was obtained in the range from 2.0 to 15.7 µmol L-1 in McIlvaine buffer solution pH 5.0. The detection and quantification limits were found to be equal to 1.33 and 4.44 µmol L-1, respectively. The developed sensors could successfully quantify PMZ in different commercial pharmaceutical formulations, with satisfactory levels of accuracy and precision. In addition to improving the analytical features of the electrodes, hemocompatibility assays carried out on erythrocytes and leukocytes showed that the AuNPs-PG do not exhibit toxic effects on the referred cells. This interesting behavior enables their use in biocompatible electrochemical sensing platforms as well as for future biomedical investigations.

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Aim: This work aimed to develop a membrane based on voriconazole (VCZ)-loaded natural rubber latex (NRL) for treating infected ulcers with Candida spp. and study their interaction, drug release, antifungal activity against Candida parapsilosis and biological characterization. Materials & methods: VCZ-loaded NRL membrane was produced by casting method. Results: Infrared spectrum showed that the incorporation of VCZ into the NRL membrane maintained its characteristics. Its mechanical properties were considered suitable for dermal application. The VCZ was able to release from NRL membrane, maintaining its antifungal activity against C. parapsilosis, besides did not present hemolytic effects. Conclusion: The VCZ-NRL membrane showed good results in mechanical, antifungal and biological assays, representing an interesting alternative to treatment of infected wound with Candida spp.

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Resumen Se presenta la síntesis de compósitos de hidroxiapatita/zirconia (HAp/ZrO2-8Y2O3) por el método de mezclado líquido en base al método de Pechini, cuya innovación radica en la obtención simultánea de ambas fases con distribución uniforme, aunque tiene la limitante de la interacción de los cationes, propiciando la formación de fases secundarias si no se controlan las variables. Los materiales fueron conformados en discos de 1 cm de diámetro y tratados a 1400 °C, para caracterizarse por espectrometría de infrarrojo (FTIR-ATR) y difracción de rayos X (DRX). Las pruebas de bioactividad fueron realizadas mediante el método de inmersión en fluidos fisiológicos simulados durante 21 días y caracterizadas por microscopia electrónica de barrido (MEB) y espectrometría de fotoelectrones emitidos por rayos X (XPS). Las pruebas de hemólisis se basaron en la norma ASTM F 756-00. Después de la inmersión, se observó la presencia de cristales de hidroxiapatita sobre la superficie del compósito, además los análisis de XPS muestran señales de energía para los elementos de calcio y fósforo. En cuanto a las pruebas de hemólisis se observaron grados de citotoxicidad por debajo del 3% con lo cual se infiere que son hemocompatibles, aunque se requieren más estudios de biocompatibilidad para su aplicación biomédica.

Abstract The synthesis of hydroxyapatite/zirconia composites (HAp/ZrO2-8Y2O3) is presented, using the liquid mixing method based on the Pechini method, whose innovation lies in the simultaneous synthesis of both phases with uniform distribution, although it has the limitation of the cations interactions, favoring the formation of secondary phases if the variables are not controlled. The obtained materials were formed into discs of 1 cm in diameter and treated at 1400 °C, and then characterized by infrared spectrometry (FTIR-ATR) and X-ray diffraction (XRD). The bioactivity tests were carried by the immersion method in simulated body fluid for 21 days and characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectrometry (XPS). The hemolysis tests were based on the ASTM F 756-00 standard. After the immersion, the presence of hydroxyapatite crystals on the surface of the composite was observed; in addition, the XPS analyzes show energy signals for the elements of calcium and phosphorus. Regarding the hemolysis tests, degrees of cytotoxicity were observed below 3%, it is inferred that they are hemocompatible, although more biocompatibility studies are required for biomedical application.

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OBJECTIVES: The PediaFlow (HeartWare International, Inc, Framingham, Mass) is a miniature, implantable, rotodynamic, fully magnetically levitated, continuous-flow pediatric ventricular assist device. The fourth-generation PediaFlow was evaluated in vitro and in vivo to characterize performance and biocompatibility. METHODS: Supported by 2 National Heart, Lung, and Blood Institute contract initiatives to address the limited options available for pediatric patients with congenital or acquired cardiac disease, the PediaFlow was developed with the intent to provide chronic cardiac support for infants as small as 3 kg. The University of Pittsburgh-led Consortium evaluated fourth-generation PediaFlow prototypes both in vitro and within a preclinical ovine model (n = 11). The latter experiments led to multiple redesigns of the inflow cannula and outflow graft, resulting in the implantable design represented in the most recent implants (n = 2). RESULTS: With more than a decade of extensive computational and experimental efforts spanning 4 device iterations, the AA battery-sized fourth-generation PediaFlow has an operating range of 0.5 to 1.5 L/min with minimal hemolysis in vitro and excellent hemocompatibility (eg, minimal hemolysis and platelet activation) in vivo. The pump and finalized accompanying implantable components demonstrated preclinical hemodynamics suitable for the intended pediatric application for up to 60 days. CONCLUSIONS: Designated a Humanitarian Use Device for "mechanical circulatory support in neonates, infants, and toddlers weighing up to 20 kg as a bridge to transplant, a bridge to other therapeutic intervention such as surgery, or as a bridge to recovery" by the Food and Drug Administration, these initial results document the biocompatibility and potential of the fourth-generation PediaFlow design to provide chronic pediatric cardiac support.

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RESUMEN Los materiales que están en contacto con el sistema corporal requieren de la característica primordial que les permita su aceptación e integración en el organismo: la biocompatibilidad. De igual manera, deben exhibir excelentes propiedades mecánicas, tribológicas y topográficas para que su prestación del servicio en el tejido especificado sea el más óptimo, pudiendo esbozar estas características mediante la caracterización de estos materiales a través de técnicas espectroscópicas y microscópicas. En el presente trabajo, una válvula artificial para el corazón fabricada en titanio y recubierta con diamond-like carbon (DLC), material altamente biocompatible, fue sometida a análisis XPS, FTIR y morfológico. En estos se encontró una alta interdifusión del recubrimiento con el sustrato junto con una gran señal de enlaces sp3. Los enlaces terminales CH3 suponen una película poco compacta. La rugosidad del recubrimiento fue baja y adecuada para fines hemocompatibles.

ABSTRACT The materials that are in contact with the body system require the fundamental characteristic that allows their acceptance and integration in the organism, the biocompatibility. Likewise, they must show excellent mechanical, tribological and morphological properties, so that their provision of a service in the specific tissue is the most optimal, being able to sketch such characteristics through the characterization of these materials by spectroscopic and microscopic techniques. In this work, an artificial valve for the heart made of titanium and coated with diamond-like carbon (DLC), highly biocompatible material, was subjected to XPS, FTIR, and morphological analysis. A high interdiffusion of the coating and the substrate was found, together with a large signal of sp3 bonds. The CH3 terminal bonds represent a little compact film. The film roughness of the coating was low and adequate for hemocompatible purposes.

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Platelets are anucleated blood cells that play an important role both in the pathogenesis of atherosclerosis and subsequent thrombosis. Dendrimers have attracted great interest in biomedical applications. However, their interactions with cell compounds and compartments are nonselective, thus causing cytotoxicity and hemotoxicity. We derivatized PAMAM G4 and G5 dendrimers to evaluate their interactions with serum metabolites, their effects on the viability of red blood cells, and their antithrombotic properties. PAMAM G4 and G5 derivatives showed better hemocompatibility than the PAMAM G4 and G5 dendrimers without any derivatization (NH2). PAMAM G4-Arginine-Tos and G4-Lysine-Cbz act as potent inhibitors of platelet aggregation induced by ADP. PAMAM G4-Arginine-Tos also showed inhibition of platelet aggregation induced by collagen, TRAP-6 and arachidonic acid. Moreover, G4-Arginine-Tos present inhibition of platelet secretion and thrombus formation under flow conditions. Based on our study, the PAMAM G4-Arginine-Tos derivative is hemocompatible and produces desirable antiplatelet and antithrombotic effects. Thus, this compound has potential applications as an antithrombotic drug or a drug delivery vehicle.

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Objective: To assess the hemocompatible performance of a novel implantable pneumatic ventricular assist device (VAD, Innovamédica, México) in healthy swine. The aim of this pilot study was first, to determine if short-term VAD implantation elicited a remarkable inflammatory response above that expected from surgical trauma; and second, to assess if heparinized or passivated VAD coatings, in combination with systemic anticoagulant or antiaggregant therapies, modified the VAD's hemocompatible performance. Methods: Hemodynamic, physiologic, inflammatory and histological parameters were measured in 27 pigs receiving VAD support for six hours, testing combinations of heparinized or passivated VAD coatings and systemic anticoagulant/ antiaggregant therapies. Mean concentrations of interleukin-1 β (IL-16), interleukin-6 (IL-6), C-reactive protein (CRP), or thrombin-antithrombin III (TAT) complexes (coagulation indicator) were measured from blood. ANOVA statistics were employed. Results: No substantial increases in mean IL-1β, IL-6, CRP, or TAT were obtained during VAD support. Hemodynamic and physiologic parameters were normal. We found no evidence of thromboembolisms or micro-infarctions in heart and lung samples. No major coaguli/deposits were found in VAD compartments. Overall, no remarkable differences in measurements were found using heparinized, passivated, or uncoated VAD, or with systemic anticoagulation, antiaggregant therapy, or no treatment. Conclusions: Our findings demonstrate, firstly, that during the time-period tested, the VAD elicited negligible inflammation above the effects of surgical trauma; and secondly, that little coagulation was observed upon VAD support in any of the cases tested. Contemplating further validation studies, our data indicate that the Innovamédica VAD is a highly hemocompatible system.

Objetivo: Evaluar la hemocompatibilidad de un nuevo dispositivo de asistencia ventricular (DAV, Innovamédica, México) neumático e implantable, en cerdos sanos. En este estudio piloto se propuso determinar primero, si la implantación a corto plazo del DAV suscitaría una respuesta inflamatoria por encima de aquella esperada tras trauma quirúrgico; segundo, evaluar si recubrimientos heparinizados o pasivos del DAV, en combinación con tratamientos sistémicos anticoagulantes o antiplaquetarios, modificarían la hemocompatibilidad del DAV. Métodos: Se midieron parámetros hemodinámicos, fisiológicos, inflamatorios e histológicos en 27 cerdos recibiendo soporte del DAV durante seis horas, evaluando combinaciones de recubrimientos heparinizados y pasivos del DAV, y terapias sistémicas anticoagulantes / antiplaquetarias. Se obtuvieron, a partir de sangre, las concentraciones promedio de interleucina-1 (IL-1β), interleucina-6 (IL-6), proteína C reactiva (PCR) y los complejos trombina-antitrombina III (TAT) (índice de coagulación). Se emplearon análisis estadísticos ANOVA. Resultados: No se observaron incrementos importantes en los niveles promedio de IL-1β, IL-6, PCR, o TAT durante soporte del DAV. Los parámetros hemodinámicos y fisiológicos fueron normales. No existió evidencia alguna de trom-boembolias o micro-infartos en muestras de miocardio y pulmón. No se encontraron coágulos o depósitos mayores en compartimentos del DAV. En general, no se apreciaron diferencias notables de mediciones utilizando dispositivos con recubrimiento heparinizado, pasivo o sin recubrimiento, en conjunto con terapia sistémica anticoagulante, antiplaquetaria o sin ella. Conclusiones: Nuestros hallazgos demuestran, primero, que durante el periodo de medición experimental, el DAV suscitó una respuesta inflamatoria mínima por encima de los efectos de trauma quirúrgico, y; segundo, en todos los casos evaluados, se observaron escasos o inexistentes efectos de coagulación durante soporte ventricular. Contemplando estudios adicionales de validación, nuestros datos indican que el DAV Innovamédica es un sistema altamente hemocompatible.

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