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BACKGROUND: Accurate diagnosis and treatment of complex cardiac tumors poses challenges, particularly when surgical resection is considered. 3D reconstruction and printing appear as a novel approach to allow heart teams for optimal surgical and post operative care. METHODS: We report two patients with uncommon masses including a cardiac angiosarcoma (CAS) and a IgG4-related disease (IgG4-RD) with exclusive cardiac involvement. In both cases, three-dimensional (3D) reconstruction and 3D-printed models were utilized to aid the surgical team achieve optimal pre-operative planning. Both patients underwent ECG-gated cardiac computed tomography angiography (CCTA) imaging and, due to the complex anatomy of the masses, their large dimensions, proximity to vital cardiac and vascular structures, and unclear etiology, computational and 3D-printed models were created for surgical planning. An exploratory literature review of studies using 3D-printed models in surgical planning was performed. RESULTS: In case 1 (CAS), due to the size and extension of the mass to the right ventricular free wall, surgical intervention was not considered curative and, during thoracotomy, an open biopsy confirmed the imaging suspicion of CAS which guided the initiation of optimal medical treatment with chemotherapy and, after clear tumor retraction, the patient underwent a second surgical intervention, and during the 18 months of follow-up showed no signs of recurrence. In Case 2 (IgG4-RD), the patient underwent uncomplicated total surgical resection; this allowed directed treatment and, at 12 months follow-up, there are no signs of recurrence. Computational and 3D-printed models were used to plan the surgery and to confirm the findings. Limited studies have explored the use of 3D printing in the surgical planning of tumors. CONCLUSIONS: We present two patients with uncommon cardiac tumors, highlighting the significant value of 3D models in the anatomical characterization and assessment of their extension. These models may be essential in surgical planning for complex cardiovascular cases and could provide more information than conventional imaging modalities. Further studies are needed to demonstrate the impact of 3D technologies in studying cardiac tumors.

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Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0 cm and a length of 11 cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering.

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Introduction: Thrombogenesis, a major cause of implantable cardiovascular device failure, can be addressed through the use of biodegradable polymers modified with anticoagulating moieties. This study introduces a novel polyester urethane urea (PEUU) functionalized with various anti-platelet deposition molecules for enhanced antiplatelet performance in regenerative cardiovascular devices. Methods: PEUU, synthesized from poly-caprolactone, 1,4-diisocyanatobutane, and putrescine, was chemically oxidized to introduce carboxyl groups, creating PEUU-COOH. This polymer was functionalized in situ with polyethyleneimine, 4-arm polyethylene glycol, seleno-L-cystine, heparin sodium, and fondaparinux. Functionalization was confirmed using Fourier-transformed infrared spectroscopy and X-ray photoelectron spectroscopy. Bio-compatibility and hemocompatibility were validated through metabolic activity and hemolysis assays. The anti-thrombotic activity was assessed using platelet aggregation, lactate dehydrogenase activation assays, and scanning electron microscopy surface imaging. The whole-blood clotting time quantification assay was employed to evaluate anticoagulation properties. Results: Results demonstrated high biocompatibility and hemocompatibility, with the most potent anti-thrombotic activity observed on pegylated surfaces. However, seleno-L-cystine and fondaparinux exhibited no anti-platelet activity. Discussion: The findings highlight the importance of balancing various factors and addressing challenges associated with different approaches when developing innovative surface modifications for cardiovascular devices.

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Vascular grafts (VGs) are medical devices intended to replace the function of a blood vessel. Available VGs in the market present low patency rates for small diameter applications setting the VG failure. This event arises from the inadequate response of the cells interacting with the biomaterial in the context of operative conditions generating chronic inflammation and a lack of regenerative signals where stenosis or aneurysms can occur. Tissue Engineered Vascular grafts (TEVGs) aim to induce the regeneration of the native vessel to overcome these limitations. Besides the biochemical stimuli, the biomaterial and the particular micro and macrostructure of the graft will determine the specific behavior under pulsatile pressure. The TEVG must support blood flow withstanding the exerted pressure, allowing the proper compliance required for the biomechanical stimulation needed for regeneration. Although the international standards outline the specific requirements to evaluate vascular grafts, the challenge remains in choosing the proper biomaterial and manufacturing TEVGs with good quality features to perform satisfactorily. In this review, we aim to recognize the best strategies to reach suitable mechanical properties in cell-free TEVGs according to the reported success of different approaches in clinical trials and pre-clinical trials.

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Fabrication of scaffolds with hierarchical structures exhibiting the blood vessel topological and biochemical features of the native extracellular matrix that maintain long-term patency remains a major challenge. Within this context, scaffold assembly using biodegradable synthetic polymers (BSPs) via electrospinning had led to soft-tissue-resembling microstructures that allow cell infiltration. However, BSPs fail to exhibit the sufficient surface reactivity, limiting protein adsorption and/or cell adhesion and jeopardizing the overall graft performance. Here, we present a methodology for the fabrication of three-layered polycaprolactone (PCL)-based tubular structures with biochemical cues to improve protein adsorption and cell adhesion. For this purpose, PCL was backbone-oxidized (O-PCL) and cast over a photolithography-manufactured microgrooved mold to obtain a bioactive surface as demonstrated using a protein adsorption assay (BSA), Fourier transform infrared spectroscopy (FTIR) and calorimetric analyses. Then, two layers of PCL:gelatin (75:25 and 95:5 w/w), obtained using a novel single-desolvation method, were electrospun over the casted O-PCL to mimic a vascular wall with a physicochemical gradient to guide cell adhesion. Furthermore, tensile properties were shown to withstand the physiological mechanical stresses and strains. In vitro characterization, using L929 mouse fibroblasts, demonstrated that the multilayered scaffold is a suitable platform for cell infiltration and proliferation from the innermost to the outermost layer as is needed for vascular wall regeneration. Our work holds promise as a strategy for the low-cost manufacture of next-generation polymer-based hierarchical scaffolds with high bioactivity and resemblance of ECM's microstructure to accurately guide cell attachment and proliferation.

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Tissue-engineered vascular grafts (TEVGs) are a promising alternative to treat vascular disease under complex hemodynamic conditions. However, despite efforts from the tissue engineering and regenerative medicine fields, the interactions between the material and the biological and hemodynamic environment are still to be understood, and optimization of the rational design of vascular grafts is an open challenge. This is of special importance as TEVGs not only have to overcome the surgical requirements upon implantation, they also need to withhold the inflammatory response and sustain remodeling of the tissue. This work aims to analyze and evaluate the bio-molecular interactions and hemodynamic phenomena between blood components, cells and materials that have been reported to be related to the failure of the TEVGs during the regeneration process once the initial stages of preimplantation have been resolved, in order to tailor and refine the needed criteria for the optimal design of TEVGs.

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Currently available small diameter vascular grafts (<6 mm) present several long-term limitations, which has prevented their full clinical implementation. Computational modeling and simulation emerge as tools to study and optimize the rational design of small diameter tissue engineered vascular grafts (TEVG). This study aims to model the correlation between mechanical-hemodynamic-biochemical variables on protein adsorption over TEVG and their regenerative potential. To understand mechanical-hemodynamic variables, two-way Fluid-Structure Interaction (FSI) computational models of novel TEVGs were developed in ANSYS Fluent 2019R3® and ANSYS Transient Structural® software. Experimental pulsatile pressure was included as an UDF into the models. TEVG mechanical properties were obtained from tensile strength tests, under the ISO7198:2016, for novel TEVGs. Subsequently, a kinetic model, linked to previously obtained velocity profiles, of the protein-surface interaction between albumin and fibrinogen, and the intima layer of the TEVGs, was implemented in COMSOL Multiphysics 5.3®. TEVG wall properties appear critical to understand flow and protein adsorption under hemodynamic stimuli. In addition, the kinetic model under flow conditions revealed that size and concentration are the main parameters to trigger protein adsorption on TEVGs. The computational models provide a robust platform to study multiparametrically the performance of TEVGs in terms of protein adsorption and their regenerative potential.

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Vascular grafts (VG) are medical devices intended to replace the function of a diseased vessel. Current approaches use non-biodegradable materials that struggle to maintain patency under complex hemodynamic conditions. Even with the current advances in tissue engineering and regenerative medicine with the tissue engineered vascular grafts (TEVGs), the cellular response is not yet close to mimicking the biological function of native vessels, and the understanding of the interactions between cells from the blood and the vascular wall with the material in operative conditions is much needed. These interactions change over time after the implantation of the graft. Here we aim to analyze the current knowledge in bio-molecular interactions between blood components, cells and materials that lead either to an early failure or to the stabilization of the vascular graft before the wall regeneration begins.

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Here, we report the genomic sequences of five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains obtained from nasopharyngeal samples from five tested coronavirus disease 2019 (COVID-19)-infected patients from the Lambayeque region in Peru during early April 2020.

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Decellularized extracellular matrices (dECMs) represent a promising alternative as a source of materials to develop scaffolds that closely mimic the native environment of cells. As a result, dECMs have attracted significant attention for their applications in regenerative medicine and tissue engineering. One such application is 3D bioprinting, in which dECMs can be used to prepare bioinks with the biomimicry attributes required for regeneration purposes. Formulating bioinks is, however, challenging, due to difficulties in assuring that the printed materials match the mechanical properties of the tissue which is to be regenerated. To tackle this issue, a number of strategies have been devised, including crosslinking methods, the addition of synthetic materials as excipients, and the use of synthetic matrices for casting. We are particularly interested in extrusion-based 3D bioprinting, mainly due to the ease of rapidly conducting tests for adjusting operating conditions such that the required rheological and mechanical properties are met when using it. Here, we propose a novel bioink that consists of an acid-based precipitation of a small intestinal submucosa (SIS) dECM. The formulated bioink also relies on photocrosslinking reactions to attempt to control gelation and ultimately the mechanical properties of the extruded material. Photoinitiation was explored with the aid of varying concentrations of riboflavin (RF). Manual extrusion and rheological flow tests confirmed the printability and shear-thinning behavior of all formulations. Photocrosslinking reactions, however, failed to promote a substantial increase in gelation, which was attributed to considerable entanglement of undigested collagen molecules. As a result, pendant amine groups thought to be involved in the photo-mediated reactions remain largely inaccessible. In silico computational fluid dynamics (CFD) simulations were implemented to determine shear stress values on the bioink along the exit of the printing nozzle. Moreover, we calculated a stability parameter as a means to estimate changes in the bioink stability during the extrusion process. Future studies should be directed toward assessing the role of temperature-induced gelation in the rheological properties of the bioink and the development of strategies to improve the efficiency of photocrosslinking processes.

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Vascular grafts are used as vascular access for hemodialysis, the most common renal replacement therapy to artificially clean blood waste after kidney malfunction. Despite that they are widely used in clinical practice, upon implantation, synthetic vasculars show complications such as thrombogenesis, reduced patency rates, low blood pressure, or even complete collapse. In this study, a C-shaped vascular graft was manufactured with small intestinal submucosa (SIS) and modified on the surface and the bulk of the material via conjugation of polyethylene glycol (PEG) to obtain a biocompatible and less thrombogenic vascular graft than the commercially available polytetrafluoroethylene (ePTFE) vascular grafts. Molecular weight and concentration of PEG molecules were systematically varied to gain insights into the underlying structure-function relationships. We analyzed the chemical, thermal, and mechanical properties of vascular grafts modified with 6 equiv of SIS-PEG 400 as well as cytotoxicity and in vitro platelet deposition. Immune response, patency rates, and extent of regeneration were also tested in vivo with the aid of swine animal models. Results showed that the conjugation levels achieved were sufficient to improve graft compliance, therefore approaching that of native vessels, while platelet deposition was altered leading to a 95% reduction compared with pristine SIS and 92% with respect to ePTFE. H&E staining on explanted samples corroborated SIS-PEG 400 biocompatibility and the ability to promote regeneration. The obtained results set solid foundations for the rational design and manufacture of a regenerative, small diameter vascular graft model and introduce an alternative to ePTFE vascular grafts for hemodialysis access.

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Despite the wide variety of tissue-engineered vascular grafts that are currently being developed, autologous vessels, such as the saphenous vein, are still the gold standard grafts for surgical treatment of vascular disease. Recently developed technologies have shown promising results in preclinical studies, but they still do not overcome the issues that native vessels present, and only a few have made the transition into clinical use. The endothelial lining is a key aspect for the success or failure of the grafts, especially on smaller diameter grafts (<5 mm). However, during the design and evaluation of the grafts, the mechanisms for the formation of this layer are not commonly examined. Therefore, a significant amount of established research might not be relevant to the clinical context, due to important differences that exist between the vascular regeneration mechanisms found in animal models and humans. This article reviews current knowledge about endothelialization mechanisms that have been so far identified: in vitro seeding, transanastomotic growth, transmural infiltration, and fallout endothelialization. Emphasis is placed on the models used for study of theses mechanisms and their effects on the development of tissue-engineering vascular conduits.

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In small intestinal submucosa (SIS) scaffolds for functional tissue engineering, the impact of scaffold fabrication parameters on cellular response and tissue regeneration may relate to the mechanotransductory properties of the final arrangement of collagen fibres. We previously proved that two fabrication parameters, (a) preservation (P) or removal (R) of a dense collagen layer present in SIS, and (b) SIS in a final dehydrated (D) or hydrated (H) state, have an effect on the micromechanical environment of SIS. In a continuation of our studies, we herein hypothesized that these fabrication parameters also modulate early mechanotransduction in cells populating the scaffold. Mechanotransduction was investigated by seeding human umbilical vein endothelial cells (HUVECs) on scaffolds, exposing them to pulsatile shear stress (12 ± 4 dyne/cm2 ) for 1 h (n = 5) in a cone-and-plate shear system, and evaluating the expression of the mechanosensitive genes Pecam1 and Enos by immunofluorescence and qPCR. Expression of mechanosensitive genes was highest in PD grafts, followed by PH and RH grafts. The RD group had similar expression to that of unsheared control cells, suggesting that the RD combination potentially reduced mechanotransduction of shear to cells. We concluded that the two fabrication parameters studied, which modify SIS micromechanics, also potentially modulated the early shear-induced expression of mechanosensitive genes in seeded HUVECs. Our findings suggest that fabrication parameters influence the outcome of SIS as a therapeutic scaffold. Copyright © 2015 John Wiley & Sons, Ltd.

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In Bi-directional Glenn (BDG) physiology, the superior systemic circulation and pulmonary circulation are in series. Consequently, only blood from the superior vena cava is oxygenated in the lungs. Oxygenated blood then travels to the ventricle where it is mixed with blood returning from the lower body. Therefore, incremental changes in oxygen extraction ratio (OER) could compromise exercise tolerance. In this study, the effect of exercise on the hemodynamic and ventricular performance of BDG physiology was investigated using clinical patient data as inputs for a lumped parameter model coupled with oxygenation equations. Changes in cardiac index, Qp/Qs, systemic pressure, oxygen extraction ratio and ventricular/vascular coupling ratio were calculated for three different exercise levels. The patient cohort (n=29) was sub-grouped by age and pulmonary vascular resistance (PVR) at rest. It was observed that the changes in exercise tolerance are significant in both comparisons, but most significant when sub-grouped by PVR at rest. Results showed that patients over 2 years old with high PVR are above or close to the upper tolerable limit of OER (0.32) at baseline. Patients with high PVR at rest had very poor exercise tolerance while patients with low PVR at rest could tolerate low exercise conditions. In general, ventricular function of SV patients is too poor to increase CI and fulfill exercise requirements. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different exercise levels according to patient specific data.

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The considerable blood mixing in the bidirectional Glenn (BDG) physiology further limits the capacity of the single working ventricle to pump enough oxygenated blood to the circulatory system. This condition is exacerbated under severe conditions such as physical activity or high altitude. In this study, the effect of high altitude exposure on hemodynamics and ventricular function of the BDG physiology is investigated. For this purpose, a mathematical approach based on a lumped parameter model was developed to model the BDG circulation. Catheterization data from 39 BDG patients at stabilized oxygen conditions was used to determine baseline flows and pressures for the model. The effect of high altitude exposure was modeled by increasing the pulmonary vascular resistance (PVR) and heart rate (HR) in increments up to 80% and 40%, respectively. The resulting differences in vascular flows, pressures and ventricular function parameters were analyzed. By simultaneously increasing PVR and HR, significant changes (p <0.05) were observed in cardiac index (11% increase at an 80% PVR and 40% HR increase) and pulmonary flow (26% decrease at an 80% PVR and 40% HR increase). Significant increase in mean systemic pressure (9%) was observed at 80% PVR (40% HR) increase. The results show that the poor ventricular function fails to overcome the increased preload and implied low oxygenation in BDG patients at higher altitudes, especially for those with high baseline PVRs. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different PVR increments.

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Perfluorocarbon (PFC) emulsions used as artificial oxygen carriers lack colloid osmotic pressure (COP) and must be administered with colloid-based plasma expanders (PEs). Although PFC emulsions have been widely studied, there is limited information about PFC emulsion interaction with PEs and blood. Their interaction forms aggregates due to electrostatic and rheological phenomena, and change blood rheology and blood flow. This study analyzes the effects of the interaction between PFC emulsions with blood in the presence of clinically-used PEs. The rheological behavior of the mixtures was analyzed in vitro in parallel with in vivo analysis of blood flow in the microcirculation using intravital microscopy, when PEs were administered in a clinically relevant scenario. The interaction between the PFC emulsion and PE with blood produced PFC droplets and red blood cell (RBCs) aggregation and increased blood viscosity in a shear dependent fashion. The PFC droplets formed aggregates when mixed with PEs containing electrolytes, and the aggregation increased with the electrolyte concentration. Mixtures of PFC with PEs that produced PFC aggregates also induced RCBs aggregation when mixed with blood, increasing blood viscosity at low shear rates. The more viscous suspension at low shear rates produced a blunted blood flow velocity profile in vivo compared to nonaggregating mixtures of PFC and PEs. For the PEs evaluated, human serum albumin produced minimal to undetectable aggregation. PFC and PEs interaction with blood can affect sections of the microcirculation with low shear rates (e.g., arterioles, venules, and pulmonary circulation) when used in a clinical setting, because persistent aggregates could cause capillary occlusion, decreased perfusion, pulmonary emboli or focal ischemia.

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Objetivo: Evaluar el efecto de la reanimación con lactato de Ringer sobre variables hemodinámicas sistémicas e intestinales en conejos sometidos a shock hemorrágico. Metodología: Se condujo un experimento animal no controlado. Se sometieron 10 conejos Nueva Zelanda a un procedimiento consistente en canalización de arteria de la oreja y de vena femoral, con posterior laparotomía y toracotomía para colocación de transductores de flujo en la base de la aorta y en arteria mesentérica superior. Se indujo hemorragia profunda de 28 mL/kg y posteriormente se hizo reanimación con Lactato de Ringer en relación de 3:1 de volumen perdido. Durante la hemorragia y la reanimación se midieron presión arterial media, fredcuencia cardiaca, gasto cardiaco (índice cardiaco), flujo sanguíneo esplácnico (índice esplácnico) y tasa de flujo intestinal-sistémica (TFIS). Resultados: La presión arterial media disminuyó durante la hemorragia, con recuperación parcial con la reanimación de líquidos. La frecuencia cardiaca aumentó con hemorragia y se estabilizó con la reanimación sin alcanzar los niveles basales. El índice cardiaco y el índice esplácnico disminuyeron significativamente durante la hemorragia y se recuperaron solo de manera parcial durante la reanimación. Sin embargo, la recuperación con respecto a valores basales del índice esplácnico (66%) fue menor que el del índice cardiaco (90%, lo cual es consistente con el comportamiento del TFIS. Conclusiones: La reanimación con Lactato de Ringer es insuficiente para restaurar la circulación esplácnica en mayor medida que para restablecer el índice cardiaco. Es posible que sea recomendable adicionar estrategias terapéuticas adicionales a la reanimación con líquidos para limitar la hipoperfusión intestinal durante shock hemorrágico.

Objective: To evaluate the effect of fluid resuscitation with lactated Ringer's solution on intestinal and systemic hemodynamic variables during hemorrhagic shock in rabbits. Methods: A controlled animal trial was conducted. Ten New Zealand rabbits underwent ear artery and femoral vein cannulation and thoraco-laparotomy in order to place flow transducers around the aortic root and superior mesenteric artery. Hemorrhage was induces up to 28 mL/kg, and then fluid resuscitation with lactated Ringer's solution was performed in a ratio 3:1 to blood loss. During hemorrhagic and resuscitation periods, mean arterial pressure, heart rate, cardiac output (cardiac index), splanchnic blood flow (splanchnic index) and intestinal to systemic flow ratio (TFIS) were measured. Results: Mean arterial pressure decreased during hemorrhage, with partial recovery during fluid resuscitation. Heart rate increased during hemorrhage and got stable during resuscitation not reaching baseline levels. On the other hand, cardiac index and splanchnic index decreased significantly during hemorrhage as well as during resuscitation. However, splanchnic index restoration with respect to baseline (66%) was significantly lower tan cardiac index restoration during fluid resuscitation, which is consistent with TFIS behavior. Conclusions: Fluid resuscitation with lactated Ringer's solution is less able to completely restore splanchnic flow as compared to systemic flow. It would be a useful recommendation to add different therapeutic strategies to fluid resuscitation to limit gut hypoperfusion during hemorrhagic shock.

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Introducción: teniendo en cuenta el envejecimiento progresivo de la población y la alta prevalencia reportada de las lesiones del manguito rotador en ese grupo etario, no es de extrañar que esta patología se convierta en un problema de salud pública. Se sabe que el aumento en el tamaño de una lesión se asocia con la aparición de síntomas, pero no existen herramientas que permitan predecir la evolución del tamaño de una lesión. Con esto en mente, se desarrolló una línea de investigación para estudiar el mecanismo de falla que inicia con la realización de un modelo tridimensional del tendón del músculo supraespinoso sano. Materiales y métodos: se caracterizó el tendón del músculo supraespinoso aplicando cargas uniaxiales en condiciones homogéneas a 7 complejos húmero-tendón-escápula cadavéricos. Con los datos obtenidos se alimentó un modelo tridimensional lineal isotrópico analizando la concentración de esfuerzos de von Mises en el tendón. Resultados: del ensayo uniaxial se obtuvieron curvas esfuerzo-deformación homogéneas para el 20% de la deformación inicial, a partir de las cuales se caracterizó el módulo de Young (14,4 ± 2,3 MPa) y el coeficiente de Poisson (0,14) del tendón. En el modelo se observó una concentración de esfuerzos en la zona central de la cara articular del tendón, cercana a su inserción. Se encontró una disminución del 5% en los esfuerzos al retirar el acromion del modelo. Discusión: se caracterizó de manera exitosa el tendón y se obtuvo un modelo tridimensional del mismo. La distribución de esfuerzos encontrada es compatible con la reportada en la literatura. El acromion no tiene mayor importancia en la magnitud de los esfuerzos en nuestro modelo. Este es el punto de partida para estudiar el mecanismo de falla.

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A viable blood substitute is still of great necessity throughout the world. Perfluorocarbon-based oxygen carriers (PFCOCs) are emulsions that take advantage of the high solubility of respiratory gases in perfluorocarbons (PFCs). Despite attractive characteristics, no PFCOC is currently approved for clinical uses. Some PFCOCs have failed due to secondary effects of the surfactants employed, like Fluosol DA, whereas others to adverse cerebrovascular effects on cardiopulmonary bypass, such as Oxygent. Further in-depth, rigorous work is needed to overcome the annotated failures and to obtain a safe PFCOC approved for human use. The aim of this study is to review in detail the most-used PFCOCs, their formulation, and preclinical and clinical trials, and to reflect upon causes of failure and strategies to overcome such failures.

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Use of occluder devices for a patent ductus arteriosus (PDA) closure is restricted to small diameter PDAs and involves high device costs. The objective of this study was to develop a new nitinol implant for the closure of a PDA and to evaluate its safety and efficacy in an animal model. The design consists of a device that promotes thrombus formation in the PDA. The device has a double-cone shape with their vertices joined. The cones are made of a nitinol wire helix with dacron fibers attached. The proximal end of the helix can be screwed to a conventional catheter release wire. In vitro testing was performed to verify the effectiveness of the implantation of the device and its releasing system; all trials (n = 30) were successful, showing accurate placement and release of the device. Complete and successful implantation of the device was achieved in all in vivo experiments (n = 5). There was one case of embolization due to premature detachment; a second device was successfully implanted. Histological evaluation after 42.3 +/- 3.1 days demonstrated complete PDA occlusion. The retrieved PDA showed total closure of the defect, endothelization of the PDA outlets and proper lodging of the device.

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