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Electronic cigarettes (e-cigs) fundamentally differ from tobacco cigarettes in their generation of liquid-based aerosols. Investigating how e-cig aerosols behave when inhaled into the dynamic environment of the lung is important for understanding vaping-related exposure and toxicity. A ventilated artificial lung model was developed to replicate the ventilatory and environmental features of the human lung and study their impact on the characteristics of inhaled e-cig aerosols from simulated vaping scenarios. Compared to static conditions, normal breathing decreased peak particle number concentrations (PNCs) and area under the curve (AUC) by 40% and 70%, respectively, and increased particle decay rates fourfold. However, even with ventilation, intrapulmonary PNC levels exceeded 2 × 106 particles/mL in a 4-puff vaping session. Both respiratory rate and tidal volume modulated e-cig aerosol exposure in a manner inversely proportional to minute ventilation. The modeled lung environment (37 °C, 88% relative humidity) also significantly altered particle size distributions by facilitating aerosol transformations such as hygroscopic growth, which further impacted e-cig aerosol exposure and particle removal. This work highlights the dynamic nature of intrapulmonary exposures and underscores the need to account for lung physiology and environmental factors when assessing inhaled e-cig aerosols. [ABSTRACT FROM AUTHOR]

Introduction: The performance of an oxygenator, as found in literature, is evaluated according to protocols that define standard values of the gas content in the inlet blood. However, when dealing with simulations of lung insufficiency, a more extensive evaluation is needed. This work aims to investigate and assess the gas exchange performance of an oxygenator for different input values of gas content in blood. Methods: Three commercially available oxygenators with different membrane surfaces were investigated in a mock loop for three blood flow rates (0.5l/min, 1l/min, and 5l/min) and two gas-to-blood ratios (1:1, and 15:1). The initial CO2 and O2 partial pressures (pCO2 and pO2) in blood were set to ≥ 100 mmHg and ≤10 mmHg, respectively. For each ratio, the efficiency, defined as the ratio between the difference of pressure inlet and outlet and the inlet pCO2 (pCO2(i)), was calculated. Results: The CO2 elimination in an oxygenator was higher for higher pCO2(i). While for a pCO2(i) of 100 mmHg, an oxygenator eliminated 80 mmHg, the same oxygenator at the same conditions eliminated 5 mmHg CO2 when pCO2(i) was 10 mmHg. The efficiency of the oxygenator decreased from 76,9% to 49,5%. For simulation reasons, the relation between the pCO2(i) and outlet (pCO2(o)) for each oxygenator at different blood and gas flows, was described as an exponential formula. Conclusion: The performance of an oxygenator in terms of CO2 elimination depends not only on the blood and gas flow, but also on the initial pCO2 value. This dependence is crucial for simulation studies in the future. [ABSTRACT FROM AUTHOR]

The hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen to and carbon dioxide from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow set of parameters that determine gas exchange efficiency and blood flow resistance, principally: fiber packing density, path length, and frontal area. These same parameters also affect thrombosis. This study investigated the effect of these parameters on clot formation using 3D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro‐rods (380 μm diameter) arranged with three packing densities (40%, 50%, and 60%) and two path lengths (2 and 4 cm). Blood was pumped through these devices corresponding to three mean blood flow velocities (16, 20, and 25 cm/min). Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of the fiber bundle enhances deposition upstream, and consequently (3) greater path length provides greater clot‐free fiber surface area for gas exchange than a shorter path length. These results can help guide the design of less thrombogenic, more efficient artificial lung designs. [ABSTRACT FROM AUTHOR]

Abstract Background Nitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators’ flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity. Methods We tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer. Results We identified three iNO-device generations based on the way they deliver NO flow: “Continuous”, “Sequential to inspiratory phase” (I-Sequential) and “Proportional to inspiratory and expiratory ventilator flow” (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations. Conclusion We identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations’ accuracy. Ventilator’s flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested.

Background: Nitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators' flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity. Methods: We tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer. Results: We identified three iNO-device generations based on the way they deliver NO flow: "Continuous", "Sequential to inspiratory phase" (I-Sequential) and "Proportional to inspiratory and expiratory ventilator flow" (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations. Conclusion: We identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations' accuracy. Ventilator's flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested. [ABSTRACT FROM AUTHOR]

Average-sized microfluidic artificial lungs consisting of rows and columns of fiber bundles with different column to row aspect ratios (AR) are numerically analyzed for flow characteristics, maximum gas transfer performance, minimum pressure drop, and proper wall shear stress (WSS) values in terms of biocompatibility. The flow is fully laminar and assumed to be incompressible and Newtonian. The transport analysis is performed using a combined convection-diffusion model, and the numerical simulations are carried out with the finite element method. The inlet volumetric flow is modeled as a sinusoidal wave function to simulate the cardiac cycle and its effect on the device performance. The model is first validated with experimental studies in steady-state condition and compared with existing correlations for transient conditions. Then, the validated model is used for a parametric study in both steady and pulsatile flow conditions. The results show that increasing the aspect ratio in fiber configuration leads to converging gas transfer, higher pressure drop, and higher WSS. While determining the optimum configuration, the acceptable shear stress levels play a decisive role to ensure biocompatibility. Also, it is observed that the steady analysis underestimates the gas transfer for higher aspect ratios. [ABSTRACT FROM AUTHOR]

Mechanical loads on the polymeric fibers of oxygenating bundles are commonly present due to bundle press-fitting during device assembly and blood pressure load. However, computational fluid dynamics (CFD) simulations for fiber bundle optimization neglect possible changes in microstructure due to such deformations. The aim of this study is to investigate the impact of fiber deformability on bundle microstructure and fluid dynamics mainly in terms of permeability. Fibers from commercial mats typically used for blood oxygenators were mechanically tested and based on these experimental data, a material model was developed to simulate the structural deformations the fibers undergo under press-fitting and blood pressure loads. Then, CFD simulations were performed on deformed bundle repetitive units to investigate permeability under varying loading conditions. The effects of different bundle geometric parameters on the variation of bundle permeability due to press-fitting were evaluated. Bundle press-fitting results in significant changes in microstructure that are reflected in a bundle permeability more than halved for a 15% press-fitting. This impact on permeability is present in all the simulated fiber bundles and becomes more pronounced as the pitch between fibers and thus bundle porosity decreases. Instead, the analyses on pressurized bundle show only small deformations caused by pressure load, with permeability changes below 1%. While blood pressure effects could be neglected, bundle press-fitting turns out to have a significant impact on bundle microstructure and permeability. Neglecting such microstructure variations during CFD simulations could also lead to incorrect assessment of the local fluid dynamics within the bundle. [ABSTRACT FROM AUTHOR]

Blood oxygenators are used to saturate oxygen levels and remove carbon dioxide from the body during cardiopulmonary bypass. Although the natural lung is hydrophilic, commercially used oxygenator materials are hydrophobic. Surface hydrophobicity weakens blood compatibility, as long‐term contact with the blood environment may lead to different degrees of blood activity. Polysulfone may be considered an alternative hydrophilic material in the design of oxygenators. Therefore, it may be directed toward developing hydrophilic membranes. This study aims to investigate the feasibility of achieving blood gas transfer with a polysulfone‐based microporous hollow fiber membrane and compare it with the commercially available polypropylene membranes. Structural differences in the membrane morphology, surface hydrophilicity, tortuosity, mass transfer rate, and material properties under different operation conditions of temperature and flow rates are reported. The polysulfone membrane has a water contact angle of 81.3°, whereas a commercial polypropylene membrane is 94.5°. The mass transfer resistances (s/m) for the polysulfone and polypropylene membranes are calculated to be 4.8 × 104 and 1.5 × 104 at 25°C, respectively. The module made of polysulfone was placed in the cardiopulmonary bypass circuit in parallel with the commercial oxygenator, and pH, pO2, pCO2 levels, and metabolic activity were measured in blood samples. [ABSTRACT FROM AUTHOR]

We demonstrate a methodology which both improves oxygen transport and reduces or eliminates bubble formation in a novel hyperbaric membrane oxygenator catheter model system. Angular oscillations were introduced to a bundle of hollow fiber membranes (HFMs) supplied with hyperbaric 100% oxygen at average gauge pressures up to 0.35 barg. Oscillating bundles enabled delivery of an oxygen flux of up to 400 mL min−1 m−2 in an aqueous solution, a doubling over a previous non-oscillating setup. Similarly, the addition of angular oscillations facilitated a five-fold reduction in pressure to achieve similar oxygen flux. The increased angular speed of oscillation improved flux, while the addition of angular micro-oscillation variations resulted in flux reductions of 7–20% compared to continuous macro-oscillation only, depending on mixing conditions. However, semi-quantitative visual observation demonstrated that angular oscillations reduced or eliminated the instance of oxygen bubble formation on the HFMs. The modeled mass transfer coefficients indicated a quasi linear relationship between rotational velocity and flux, suggesting that faster oscillation speeds could further improve oxygen mass transport allowing for HFM bundles to maintain high oxygen fluxes while eliminating bubble formation. This encourages further development of our compact oxygenating catheter that could be used intravascularly. [ABSTRACT FROM AUTHOR]

Purpose: Fulminant myocarditis presents as acute severe heart failure and requires mechanical cardiocirculatory support. Left-ventricular (LV) decompression is necessary for the successful recovery of these patients. This retrospective study aimed to evaluate the functional outcomes of providing central extracorporeal membrane oxygenation (ECMO) with LV decompression for the treatment of refractory fulminant myocarditis. Methods: Between January 2015 and February 2021, seven consecutive fulminant myocarditis patients (mean age: 41.1 ± 26.1 years) received central ECMO support with transapical LV decompression, with an 18 French cannula integrated into the ECMO circuit in a Y-fashion. The baseline characteristics and postoperative outcomes of the patients were collected. Results: On admission, all patients received prior peripheral ECMO, and 85.7% (6/7) of patients received prior intra-aortic balloon pumping. However, all patients had refractory cardiogenic shock that failed prior to decompression. Six patients recovered successfully after a mean ECMO support of 20.0 ± 11.5 days and five patients had no recurrence of cardiac decompensation. The mean ICU and mean hospital stays were 36.7 ± 23.5 days and 60.6 ± 24.9 days, respectively. Hospital mortality was 28.6% (2/7). Two patients died due to sepsis and stroke during hospitalization. Conclusions: Central ECMO with an LV vent was effective for fulminant myocarditis refractory to percutaneous cardiopulmonary support therapy and other therapies. [ABSTRACT FROM AUTHOR]

Julia Dormann,1 Sebastian Wendt,1 Michael Dreher,2 Kelly Ansems,1 Carole Rolland,3 Jan Spillner,4 Agnieszka Szafran,1 Thomas Breuer,1 Christophe Pison,5– 7,&ast; Tom Verbelen,8,&ast; Carina Benstoem1,&ast; 1Department of Intensive Care Medicine and Intermediate Care, Medical Faculty, RWTH Aachen University, Aachen, Germany; 2Department of Pneumology and Intensive Care Medicine, RWTH Aachen University, Aachen, Germany; 3Techniques de l’Ingénierie Médicale et de la Complexité (TIMC), Centre National de la Recherche Scientifique (CNRS), University Grenoble Alpes, Grenoble, France; 4Department of Thoracic Surgery, Medical Faculty, RWTH Aachen University, Aachen, Germany; 5Department of Pneumology and Physiology, CHU Grenoble Alpes; University Grenoble Alpes, Grenoble, France; 6Laboratory of Fundamental and Applied Bioenergetics, LBFA, Inserm1055, Grenoble, France; 7Département Universitaire des Patients Grenoble Alpes, University Grenoble Alpes, Grenoble, France; 8Department of Cardiovascular Sciences, KU Leuven and Department of Cardiac Surgery, University Hospitals Leuven, Leuven, Belgium&ast;These authors contributed equally to this workCorrespondence: Carina Benstoem, Department of Intensive Care Medicine and Intermediate Care, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, Aachen, D-52074, Tel +49 241 80 38038, Fax +49 241 80 33 82182, Email cbenstoem@ukaachen.deBackground: Terminal lung diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) in progression cause a large reduction in quality of life and may lead to bilateral lung transplantation (bLTx). An artificial portable lung could provide a bridge to lung transplantation, allowing patients to remain at home and mobile for longer. To advance the development of such an artificial lung, patient feedback is essential. The aim of this study is to analyze patient acceptance about an extracorporeal artificial lung and to implement these findings into the development.Methods: In collaboration with a medical device developer, we presented a portable dummy oxygenator to patients with advanced lung disease, as potential end users. Data collection in Germany and France was based on two different methods: an online questionnaire and face-to-face interviews (F2F).Results: A total of 604 participants answered the online questionnaire and 17 participants were included in the F2F interviews. The majority of participants (COPD n=140, PH n=17) were able to walk more than 1 km with a mean suffering pressure of 2.87 and 3, respectively. Six of the 17 F2F participants who could walk < 1 km were interested in an assistive device. The statistical value of Fisher’s exact test for suffering pressure and desire for a portable oxygenator was 0.45.Conclusion: In patients with advanced lung disease, there is no statistically significant association between subjectively increased suffering pressure and desire for a portable oxygenator, so market introduction may be difficult. Potential end users should be implemented early in device development. Data collection via an online questionnaire combined with personal interviews has proven to be a successful approach here.Keywords: chronic obstructive pulmonary disease, pulmonary hypertension, artificial lung, patient feedback

When returning blood to the pulmonary artery (PA), the inflow jet interferes with local hemodynamics. We investigated the consequences for several connection scenarios using transient computational fluid dynamics simulations. The PA was derived from CT data. Three aspects were varied: graft flow rate, anastomosis location, and inflow jet path length from anastomosis site to impingement on the PA wall. Lateral anastomosis locations caused abnormal flow distribution between the left and right PA. The central location provided near-physiological distribution but induced higher wall shear stress (WSS). All effects were most pronounced at high graft flows. A central location is beneficial regarding flow distribution, but the resulting high WSS might promote detachment of local thromboembolisms or influence the autonomic nervous innervation. Lateral locations, depending on jet path length, result in lower WSS at the cost of an unfavorable flow distribution that could promote pulmonary vasculature changes. Case-specific decisions and further research are necessary. [ABSTRACT FROM AUTHOR]

Extracorporeal life support is an advanced therapy that circulates blood through an extracorporeal oxygenator, performing gas exchange outside the body. However, its use is limited by severe complications, including bleeding, clotting, and hemolysis. Semiconductor silicon-based membranes have emerged as an alternative to traditional hollow-fiber semipermeable membranes. These membranes offer excellent gas exchange efficiency and the potential to increase hemocompatibility by improving flow dynamics. In this work, we evaluate two next-generation silicon membrane designs, which are intended to be mechanically robust and efficient in gas exchange, while simultaneously reducing fabrication complexity. The "window" design features 10 µm pores on one side and large windows on the back side. The "cavern" design also uses 10 µm pores but contains a network of interconnected buried caverns to distribute the sweep gas from smaller inlet holes. Both designs were shown to be technically viable and able to be reproducibly fabricated. In addition, they both were mechanically robust and withstood 30 psi of transmembrane pressure without breakage or bubbling. At low sweep gas pressures, gas transfer efficiency was similar, with the partial pressure of oxygen in water increasing by 10.7 ± 2.3 mmHg (mean ± standard deviation) and 13.6 ± 1.9 mmHg for the window and cavern membranes, respectively. Gas transfer efficiency was also similar at higher pressures. At 10 psi, oxygen tension increased by 16.8 ± 5.7 mmHg (window) and 18.9 ± 1.3 mmHg (cavern). We conclude that silicon membranes featuring a 10 µm pore size can simplify the fabrication process and improve mechanical robustness while maintaining excellent efficiency. [ABSTRACT FROM AUTHOR]

Traditional in vitro and in vivo models for inhalation toxicology studies often fail to replicate the anatomical and physiological conditions of the human lung. This limitation hinders our understanding of intrapulmonary exposures and their related health effects. To address this gap, we developed a ventilated artificial lung system that replicates human inhalation exposures in four key aspects: (1) facilitating continuous breathing with adjustable respiratory parameters; (2) distributing inhaled aerosols through transitional airflow fields in 3D-printed airway structures, which enables size-dependent particle deposition; (3) duplicating the warm and humid lung environment to promote inhaled aerosol dynamics, such as hygroscopic growth; and (4) supporting the cultivation of human airway epithelium for aerosol exposure and toxicological analyses. As a proof-of-concept application, we exposed human bronchial epithelial cells to electronic cigarette aerosols in the system. Our results show that electronic cigarette particles undergo significant hygroscopic growth within the artificial lung, leading to a 19% greater deposition dose compared to data collected at room temperature and relative humidity. Additionally, short-term exposure altered epithelial production of the chemokine Fractalkine in a nicotine-dependent manner, but no acute toxic effects were observed. This artificial lung system provides a more physiologically relevant in vitro model for studying inhalation exposures.

For children with end-stage lung disease that cannot wean from extracorporeal life support (ECLS), a wearable artificial lung would permit extubation and provide a bridge to recovery or transplantation. We evaluate the function of the novel Pediatric MLung—a low-resistance, pumpless artificial lung developed specifically for children—in healthy animal subjects. Adolescent "mini sheep" weighing 12–20 kg underwent left thoracotomy, cannulation of the main pulmonary artery (PA; inflow) and left atrium (outflow), and connection to the MLung. Thirteen sheep were studied; 6 were supported for 7 days. Mean PA pressure was 23.9 ± 6.9 mmHg. MLung blood flow was 633±258 mL/min or 30.0 ± 16.0% of CO. MLung pressure drop was 4.4 ± 3.4 mmHg. Resistance was 7.2 ± 5.2 mmHg/L/min. Device outlet oxygen saturation was 99.0 ± 3.3% with inlet saturation 53.8 ± 7.3%. Oxygen delivery was 41.1 ± 18.4 mL O 2 /min (maximum 84.9 mL/min) or 2.8 ± 1.5 mL O 2 /min/kg. Platelet count significantly decreased; no platelet transfusions were required. Plasma free hemoglobin significantly increased only on day 7, at which point 2 of the animals had plasma free hemoglobin levels above 50 mg/dL. The MLung provides adequate gas exchange at appropriate blood flows for the pediatric population in a PA-to-LA configuration. Further work remains to improve the biocompatibility of the device. N/A [ABSTRACT FROM AUTHOR]

The artificial lung (AL) technology is one of the membrane-based artificial organs that partly augments lung functions, i.e. blood oxygenation and CO 2 removal. It is generally employed as an extracorporeal membrane oxygenation (ECMO) device to treat acute and chronic lung-failure patients, and the recent outbreak of the COVID-19 pandemic has re-emphasized the importance of this technology. The principal component in AL is the polymeric membrane oxygenator that facilitates the O 2 /CO 2 exchange with the blood. Despite the considerable improvement in anti-thrombogenic biomaterials in other applications (e.g., stents), AL research has not advanced at the same rate. This is partly because AL research requires interdisciplinary knowledge in biomaterials and membrane technology. Some of the promising biomaterials with reasonable hemocompatibility — such as emerging fluoropolymers of extremely low surface energy - must first be fabricated into membranes to exhibit effective gas exchange performance. As AL membranes must also demonstrate high hemocompatibility in tandem, it is essential to test the membranes using in-vitro hemocompatibility experiments before in-vivo test. Hence, it is vital to have a reliable in-vitro experimental protocol that can be reasonably correlated with the in-vivo results. However, current in-vitro AL studies are unsystematic to allow a consistent comparison with in-vivo results. More specifically, current literature on AL biomaterial in-vitro hemocompatibility data are not quantitatively comparable due to the use of unstandardized and unreliable protocols. Such a wide gap has been the main bottleneck in the improvement of AL research, preventing promising biomaterials from reaching clinical trials. This review summarizes the current state-of-the-art and status of AL technology from membrane researcher perspectives. Particularly, most of the reported in-vitro experiments to assess AL membrane hemocompatibility are compiled and critically compared to suggest the most reliable method suitable for AL biomaterial research. Also, a brief review of current approaches to improve AL hemocompatibility is summarized. The importance of Artificial Lung (AL) technology has been re-emphasized in the time of the COVID-19 pandemic. The utmost bottleneck in the current AL technology is the poor hemocompatibility of the polymer membrane used for O 2 /CO 2 gas exchange, limiting its use in the long-term. Unfortunately, most of the in-vitro AL experiments are unsystematic, irreproducible, and unreliable. There are no standardized in-vitro hemocompatibility characterization protocols for quantitative comparison between AL biomaterials. In this review, we tackled this bottleneck by compiling the scattered in-vitro data and suggesting the most suitable experimental protocol to obtain reliable and comparable hemocompatibility results. To the best of our knowledge, this is the first review paper focusing on the hemocompatibility challenge of AL technology. [Display omitted] [ABSTRACT FROM AUTHOR]

The use of extracorporeal oxygenation and CO2 removal has gained clinical validity and popularity in recent years. These systems are composed of a pump to drive blood flow through the circuit and a hollow fiber membrane bundle through which gas exchange is achieved. Mathematical modeling of device design is utilized by researchers to improve device hemocompatibility and efficiency. A previously published mathematical model to predict CO2 removal in hollow fiber membrane bundles was modified to include an empirical representation of the Haldane effect. The predictive capabilities of both models were compared to experimental data gathered from a fiber bundle of 7.9 cm in length and 4.4 cm in diameter. The CO2 removal rate predictions of the model including the Haldane effect reduced the percent error between experimental data and mathematical predictions by up to 16%. Improving the predictive capabilities of computational fluid dynamics for the design of hollow fiber membrane bundles reduces the monetary and manpower expenses involved in designing and testing such devices. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas-permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water-based bench-top set-up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM-PDMS membranes was 3.03 ± 0.42 mL O2 min-1 m-2 cm Hg-1 with pure water and 1.71 ± 1.03 mL O2 min-1 m-2 cm Hg-1 with blood. An analytic model to predict gas transport was developed using data from the bench-top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM-PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators.

The increasing prevalence of chronic lung disease worldwide, combined with the emergence of multiple pandemics arising from respiratory viruses over the past century, highlights the need for safer and efficacious means for providing artificial lung support. Mechanical ventilation is currently used for the vast majority of patients suffering from acute and chronic lung failure, but risks further injury or infection to the patient's already compromised lung function. Extracorporeal membrane oxygenation (ECMO) has emerged as a means of providing direct gas exchange with the blood, but limited access to the technology and the complexity of the blood circuit have prevented the broader expansion of its use. A promising avenue toward simplifying and minimizing complications arising from the blood circuit, microfluidics‐based artificial organ support, has emerged over the past decade as an opportunity to overcome many of the fundamental limitations of the current standard for ECMO cartridges, hollow fiber membrane oxygenators. The power of microfluidics technology for this application stems from its ability to recapitulate key aspects of physiological microcirculation, including the small dimensions of blood vessel structures and gas transfer membranes. An even greater advantage of microfluidics, the ability to configure blood flow patterns that mimic the smooth, branching nature of vascular networks, holds the potential to reduce the incidence of clotting and bleeding and to minimize reliance on anticoagulants. Here, we summarize recent progress and address future directions and goals for this potentially transformative approach to artificial lung support. Correspondence between native blood vessel branching and the microfluidic blood vessel branching patterns that form the design basis for bio‐inspired artificial organs. As in the physiological vasculature, a large inlet vessel branches into multiple trunk lines, each of which leads to further branching into smaller microchannels. This design paradigm preserves a smooth distribution of blood flow throughout the microfluidic network. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the emergence of various high-quality membrane materials, the selection of suitable membrane materials has become the key to the development of artificial lung technology. The surface modification of membrane materials by physical or chemical methods to prepare composite membranes with excellent performance such as good blood compatibility and high gas exchange rate is a hot topic in current research. OBJECTIVE: Based on the development process of artificial lung, the commonly used membrane materials were introduced, and the research results of improving the blood compatibility of membrane materials were reviewed, and the new direction of improving the hollow fiber membrane materials for artificial lung in the future was proposed. METHODS: The articles related to artificial lung membrane materials published on Pub Med database, CN Kl database and Wanfang database were searched, and the articles were read and screened. Key words in English and Chinese were "artificial lung; membrane artificial lung; oxygenator; hollow fiber membrane; polymer; blood compatibility". RESULTS AND CONCLUSION: In recent years, various kinds of molecules that can improve blood compatibility have been used by researchers to improve the surface of membrane materials of membrane artificial lung. Studies on modified membrane materials such as heparin, hydrophilic molecules (such as polyethylene glycol) and amphoteric molecules (such as phosphocholine) are relatively mature and have been widely used in clinical practice. Other improvement measures (such as surface endothelialization, NO release hollow fiber) are also gradually developed. However, there are few studies on improving the gas exchange capacity of membrane materials, and there is still room for further improvement and optimization in oxygenation performance. In the future, the research of artificial lung membrane materials will develop in two directions: one is to develop the surface modified coating of mixed membrane materials to maximize blood compatibility by combining the advantages of various materials. Second, the gas exchange oxygenation performance of membrane materials can be improved and plasma leakage can be avoided by improving hemodynamics, improving membrane making process, physical or chemical modification and other methods. [ABSTRACT FROM AUTHOR]

Purpose: Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. Methods: An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration ("pulsed delivery"), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5–40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. Results: Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 ± 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. Conclusion: Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) provides pulmonary and/or cardiac support for critically ill patients. Due to their diseases, they are at high risk of developing acute kidney injury. In that case, continuous renal replacement therapy (CRRT) is applied to provide renal support and fluid management. The ECMO and CRRT circuits can be combined by an integrated or parallel approach. So far, all methods used for combined extracorporeal lung and kidney support present serious drawbacks. This includes not only high risks of circuit related complications such as bleeding, thrombus formation, and hemolysis, but also increase in technical workload and health care costs. In this sense, the development of a novel optimized artificial lung device with integrated renal support could offer important treatment benefits. Therefore, we conducted a review to provide technical background on existing techniques for extracorporeal lung and kidney support and give insight on important aspects to be addressed in the development of this novel highly integrated artificial lung device.

In end-stage lung diseases, the shortage of donor lungs for transplantation and long waiting lists are the main culprits in the significantly increasing number of patient deaths. New strategies to curb this issue are being developed with the help of recent advancements in bioengineering technology, with the generation of lung scaffolds as a steppingstone. There are various types of lung scaffolds, namely, acellular scaffolds that are developed via decellularization and recellularization techniques, artificial scaffolds that are synthesized using synthetic, biodegradable, and low immunogenic materials, and hybrid scaffolds which combine the advantageous properties of materials in the development of a desirable lung scaffold. There have also been advances in the design of bioreactors in terms of providing an optimal regenerative environment for the maturation of functional lung tissue over time. In this review, the emerging paradigms in the field of lung tissue bioengineering will be discussed. [ABSTRACT FROM AUTHOR]

Background: Membranes based on triply periodic minimal surfaces (TPMS) have proven a superior gas transfer compared to the contemporary hollow fiber membrane (HFM) design in artificial lungs. The improved oxygen transfer is attributed to disrupting the laminar boundary layer adjacent to the membrane surface known as main limiting factor to mass transport. However, it requires experimental proof that this improvement is not at the expense of greater damage to the blood. Hence, the aim of this work is a valid statement regarding the structure‐dependent hemolytic behavior of TPMS structures compared to the current HFM design. Methods: Hemolysis tests were performed on structure samples of three different kind of TPMS‐based designs (Schwarz‐P, Schwarz‐D and Schoen's Gyroid) in direct comparison to a hollow fiber structure as reference. Results: The results of this study suggest that the difference in hemolysis between TPMS membranes compared to HFMs is small although slightly increased for the TPMS membranes. There is no significant difference between the TPMS structures and the hollow fiber design. Nevertheless, the ratio between the achieved additional oxygen transfer and the additional hemolysis favors the TPMS‐based membrane shapes. Conclusion: TPMS‐shaped membranes offer a safe way to improve gas transfer in artificial lungs. [ABSTRACT FROM AUTHOR]

Surface modification of hemocompatible copolymers on silicone elastomers (SEs) is crucial for the long-term use of medical devices. Both physical adsorption and chemical conjugation are important for modification of SE. Oxygen plasma treatment is widely used to produce silanol groups on SE for silane coupling. However, the plasma reaction is difficult to apply to the surface modification of three-dimensional complex devices. This study demonstrated an appropriate and efficient method with alkaline solution for producing silanol groups on SE for modifying phosphorylcholine-based copolymer with organosilane (cross-MPC copolymer). A 2.5 wt% aqueous solution of potassium hydroxide (KOH) was effective in producing silanol groups and for coating the cross-MPC copolymer. Additionally, we successfully modified the cross-MPC copolymer on the inner surface of SE tubes after pretreatment with the 2.5 wt% KOH aqueous solution, and the copolymer film was coated homogeneously. The cross-MPC copolymer film on SE was stable for one month under fluidic condition with a shear stress of 3.2 Pa. The hollow fiber membrane with the polymer coating inhibited blood coagulation after one week implantation with extracorporeal circulation device using a goat. Therefore, pretreatment of SE using an alkaline solution is an appropriate method for producing silanol groups for coating the cross-MPC copolymer by silane-coupling reaction.

Artificial lungs have the potential to serve as a bridge to transplantation or recovery for children with end-stage lung disease dependent on extracorporeal life support, but such devices currently require systemic anticoagulation. We describe our experience using the novel Nitric Oxide (NO) Surface Anticoagulation (NOSA) system—an NO-releasing circuit with NO in the sweep gas—with the Pediatric MLung—a low-resistance, pumpless artificial lung. NO flux testing: MLungs (n = 4) were tested using veno-venous extracorporeal life support in a sheep under anesthesia with blood flow set to 0.5 and 1 L/min and sweep gas blended with 100 ppm NO at 1, 2, and 4 L/min. NO and NO 2 were measured in the sweep and exhaust gas to calculate NO flux across the MLung membrane. Pumpless implants: Sheep (20–100 kg, n = 3) underwent thoracotomy and cannulation via the pulmonary artery (device inflow) and left atrium (device outflow) using cannulae and circuit components coated with an NO donor (diazeniumdiolated dibutylhexanediamine; DBHD-N 2 O 2) and argatroban. Animals were connected to the MLung with 100 ppm NO in the sweep gas under anesthesia for 24 h with no systemic anticoagulation after cannulation. NO flux testing: NO flux averaged 3.4 ± 1.0 flux units (x10−10 mol/cm2/min) (human vascular endothelium: 0.5–4 flux units). Pumpless implants: 3 sheep survived 24 h with patent circuits. MLung blood flow was 716 ± 227 mL/min. Outlet oxygen saturation was 98.3 ± 2.6%. Activated clotting time was 151±24 s. Platelet count declined from 334,333 ± 112,225 to 123,667 ± 7,637 over 24 h. Plasma free hemoglobin and leukocyte and platelet activation did not significantly change. The NOSA system provides NO flux across a gas-exchange membrane of a pumpless artificial lung at a similar rate as native vascular endothelium and achieves effective local anticoagulation of an artificial lung circuit for 24 h. [ABSTRACT FROM AUTHOR]

Membranes for use in high gas exchange lung applications are riddled with fouling. The goal of this research is to create a membrane that can function in an artificial lung until the actual lung becomes available for the patient. The design of the artificial lung is based on new hollow fiber membranes (HFMs), due to which the current devices have short and limited periods of low fouling. By successfully modifying membranes with attached peptoids, low fouling can be achieved for longer periods of time. Hydrophilic modification of porous polysulfone (PSF) membranes can be achieved gradually by polydopamine (PSU-PDA) and peptoid (PSU-PDA-NMEG5). Polysulfone (PSU-BSA-35Mg), polysulfone polydopamine (PSUPDA-BSA-35Mg) and polysulfone polydopamine peptoid (PSU-PDA-NMEG5-BSA35Mg) were tested by potting into the new design of gas exchange modules. Both surfaces of the modified membranes were found to be highly resistant to protein fouling permanently. The use of different peptoids can facilitate optimization of the low fouling on the membrane surface, thereby allowing membranes to be run for significantly longer time periods than has been currently achieved. [ABSTRACT FROM AUTHOR]

Artificial lung technology is advancing at a startling rate raising hopes that it would better serve the needs of those requiring respiratory support. Whether to assist the healing of an injured lung, support patients to lung transplantation, or to entirely replace native lung function, safe and effective artificial lungs are sought. After 200 years of bioengineering progress, artificial lungs are closer than ever before to meet this demand which has risen exponentially due to the COVID-19 crisis. In this review, the critical advances in the historical development of artificial lungs are detailed. The current state of affairs regarding extracorporeal membrane oxygenation, intravascular lung assists, pump-less extracorporeal lung assists, total artificial lungs, andmicrofluidic oxygenators are outlined. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) has been used clinically for more than 40 years as a bridge to transplantation, with hollow-fiber membrane (HFM) oxygenators gaining in popularity due to their high gas transfer and low flow resistance. In spite of the technological advances in ECMO devices, the inevitable contact of the perfused blood with the polymer hollow-fiber gas-exchange membrane, and the subsequent thrombus formation, limits their clinical usage to only 2-4?weeks. In addition, the inhomogeneous flow in the device can further enhance thrombus formation and limit gas-transport efficiency. Endothelialization of the blood contacting surfaces of ECMO devices offers a potential solution to their inherent thrombogenicity. However, abnormal shear stresses and inhomogeneous blood flow might affect the function and activation status of the seeded endothelial cells (ECs). In this study, the blood flow through two HFM oxygenators, including the commercially available iLA® MiniLung Petite Novalung (Xenios AG, Germany) and an experimental one for the rat animal model, was modeled using computational fluid dynamics (CFD), with a view to assessing the magnitude and distribution of the wall shear stress (WSS) on the hollow fibers and flow fields in the oxygenators. This work demonstrated significant inhomogeneity in the flow dynamics of both oxygenators, with regions of high hollow-fiber WSS and regions of stagnant flow, implying a variable flow-induced stimulation on seeded ECs and possible EC activation and damage in a biohybrid oxygenator setting. [ABSTRACT FROM AUTHOR]

Abstract Background There is increasing evidence demonstrating the value of partial extracorporeal CO2 removal (ECCO2R) for the treatment of hypercapnia in patients with acute exacerbations of chronic obstructive pulmonary disease and acute respiratory distress syndrome. Mechanical ventilation has traditionally been used to treat hypercapnia in these patients, however, it has been well-established that aggressive ventilator settings can lead to ventilator-induced lung injury. ECCO2R removes CO2 independently of the lungs and has been used to permit lung protective ventilation to prevent ventilator-induced lung injury, prevent intubation, and aid in ventilator weaning. The Low-Flow Pittsburgh Ambulatory Lung (LF-PAL) is a low-flow ECCO2R device that integrates the fiber bundle (0.65 m2) and centrifugal pump into a compact unit to permit patient ambulation. Methods A blood analog was used to evaluate the performance of the pump at various impeller rotation rates. In vitro CO2 removal tested under normocapnic conditions and 6-h hemolysis testing were completed using bovine blood. Computational fluid dynamics and a mass-transfer model were also used to evaluate the performance of the LF-PAL. Results The integrated pump was able to generate flows up to 700 mL/min against the Hemolung 15.5 Fr dual lumen catheter. The maximum vCO2 of 105 mL/min was achieved at a blood flow rate of 700 mL/min. The therapeutic index of hemolysis was 0.080 g/(100 min). The normalized index of hemolysis was 0.158 g/(100 L). Conclusions The LF-PAL met pumping, CO2 removal, and hemolysis design targets and has the potential to enable ambulation while on ECCO2R.

Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including artificial lung technology. This invited review discusses ongoing developments and future research pathways for respiratory assist devices and tissue engineering to treat advanced and refractory lung disease. An overview is also given on the aftermath of the coronavirus disease 2019 pandemic and lessons learned as the world comes out of this situation. The first order of business in the future of lung support is solving the problems with existing mechanical devices. Interestingly, challenges identified during the early days of development persist today. These challenges include device‐related infection, bleeding, thrombosis, cost, and patient quality of life. The main approaches of the future directions are to repair, restore, replace, or regenerate the lungs. Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems and can be used to bridge lung failure patients to transplantation. Progress in the development of microchannel‐based devices has provided the concept of biomimetic devices that may even enable intracorporeal implantation. Tissue engineering and cell‐based technologies have provided the concept of bioartificial lungs with properties similar to the native organ. Recent progress in artificial lung technologies includes continued advances in both engineering and biology. The final goal is to achieve a truly implantable and durable artificial lung that is applicable to destination therapy. [ABSTRACT FROM AUTHOR]

Purpose: Currently used cannulae for extracorporeal carbon dioxide removal (ECCO2R) are associated with complications such as thrombosis and distal limb ischemia, especially for long-term use. We hypothesize that the risk of these complications is reducible by attaching hemodynamically optimized grafts to the patient's vessels. In this study, as a first step towards a long-term stable ECCO2R connection, we investigated the feasibility of a venovenous connection to the common iliac veins. To ensure its applicability, the drainage of reinfused blood (recirculation) and high wall shear stress (WSS) must be avoided. Methods: A reference model was selected for computational fluid dynamics, on the basis of the analysis of imaging data. Initially, a sensitivity analysis regarding recirculation was conducted using as variables: blood flow, the distance of drainage and return to the iliocaval junction, as well as the diameter and position of the grafts. Subsequently, the connection was optimized regarding recirculation and the WSS was evaluated. We validated the simulations in a silicone model traversed by dyed fluid. Results: The simulations were in good agreement with the validation measurements (mean deviation 1.64%). The recirculation ranged from 32.1 to 0%. The maximum WSS did not exceed 5.57 Pa. The position and diameter of the return graft show the highest influence on recirculation. A correlation was ascertained between recirculation and WSS. Overall, an inflow jet directed at a vessel wall entails not only high WSS, but also a flow separation and thereby an increased recirculation. Therefore, return grafts aligned to the vena cava are crucial. Conclusion: In conclusion, a connection without recirculation could be feasible and therefore provides a promising option for a long-term ECCO2R connection. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) has become a mainstay of therapy for patients suffering from severe respiratory failure. Ambulatory ECMO systems aim to provide long‐term out‐of‐hospital respiratory support. As a patient's activity level changes, the required level of ECMO support varies with oxygen consumption and metabolic fluctuations. To compensate for such changes, an autoregulatory ECMO system (AR‐ECMO) has been developed and its performance was evaluated as a proof of concept in an acute ovine model. The AR‐ECMO system consists of a regular ECMO circuit and an electromechanical control system. A custom fuzzy logic control algorithm was implemented to adjust the blood flow and sweep gas flow of the ECMO circuit to meet the varying respiratory demand by utilizing two noninvasive sensors for venous oxyhemoglobin saturation and the oxygenator exhaust gas CO2 concentration. Disturbance responses of the AR‐ECMO to induced acute respiratory distress were assessed for six hours in four juvenile sheep cannulated with a veno‐pulmonary artery ECMO configuration, including acute ventilator shutoff, ventilator step change (off‐on‐off), and forced desaturation. All sheep survived for the study duration. The AR‐ECMO system was able to respond and maintain stable hemodynamics and physiological blood gas contents (SpO2 = 96.3 % ± 4.29, pH 7.44 ± 0.09, pCO2 = 38.9 ± 9.9 mm Hg, and pO2 =237.9 ± 123.6 mm Hg) during simulated respiratory distress. Acceptable correlation between oxygenator exhaust gas CO2 and oxygenator outlet pCO2 were observed (R2 = 0.84). In summary, the AR‐ECMO system successfully maintained physiologic control of peripheral oxygenation and carbon dioxide over the study period, utilizing only measurements taken directly from the ECMO circuit. The range of system response necessitates an adaptable system in the setting of variable metabolic demands. The ability of this system to respond to significant disturbances in ventilator support is encouraging. Future work to evaluate our AR‐ECMO system in long‐term, awake animal studies is necessary for further refinement. [ABSTRACT FROM AUTHOR]

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has emerged as a potential life-saving treatment for patients with acute respiratory failure. Given the accumulating literature supporting the use of VV-ECMO without therapeutic levels of anticoagulation, it might be feasible to use it for planned intubation before surgical procedures. Here, we report consecutive series of patients who underwent planned initiation of VV-ECMO, without anticoagulation, before induction of general anesthesia for anticipated difficult airways or respiratory decompensation. We describe the approach to safely initiate VV-ECMO in an awake patient. We retrospectively identified patients in a prospectively maintained database who underwent planned initiation of VVECMO before intubation. Standard statistical methods were used to determine post-procedure outcomes. Patients included were three men and one woman, with a mean age of 34.3 6 10.4 years. Indications included mediastinal lymphoma, foreign body obstruction, hemoptysis, and tracheo-esophageal fistula. VV-ECMO was initiated electively for all patients, and no anticoagulation was used. The median duration of VV-ECMO support was 2.5 days (1-11 days), the median length of ventilator dependence and intensive care unit stay was 1 day (1-23 days) and 5 days (4-31 days), respectively. The median length of stay was 18.5 days (8-39 days). There were no thrombotic complications and no mortality at 30 days. Initiation of awake VV-ECMO is feasible and is safe before intubation and induction of anesthesia in patients at high risk for respiratory decompensation. [ABSTRACT FROM AUTHOR]

Abstract Background Extracorporeal carbon dioxide removal (ECCO2R) systems have gained clinical appeal as supplemental therapy in the treatment of acute and chronic respiratory injuries with low tidal volume or non-invasive ventilation. We have developed an ultra-low-flow ECCO2R device (ULFED) capable of operating at blood flows comparable to renal hemodialysis (250 mL/min). Comparable operating conditions allow use of minimally invasive dialysis cannulation strategies with potential for direct integration to existing dialysis circuitry. Methods A carbon dioxide (CO2) removal device was fabricated with rotating impellers inside an annular hollow fiber membrane bundle to disrupt blood flow patterns and enhance gas exchange. In vitro gas exchange and hemolysis testing was conducted at hemodialysis blood flows (250 mL/min). Results In vitro carbon dioxide removal rates up to 75 mL/min were achieved in blood at normocapnia (pCO2 = 45 mmHg). In vitro hemolysis (including cannula and blood pump) was comparable to a Medtronic Minimax oxygenator control loop using a time-of-therapy normalized index of hemolysis (0.19 ± 0.04 g/100 min versus 0.12 ± 0.01 g/100 min, p = 0.169). Conclusions In vitro performance suggests a new ultra-low-flow extracorporeal CO2 removal device could be utilized for safe and effective CO2 removal at hemodialysis flow rates using simplified and minimally invasive connection strategies.

Background: A subset of patients with COVID-19 acute respiratory distress syndrome (ARDS) require extracorporeal membrane oxygenation (ECMO). Veno-pulmonary (VP) ECMO provides support to the right ventricle and decreased risk of recirculation., Methods: A retrospective analysis of patients with COVID-19 ARDS and VP ECMO was performed. Patients were separated into groups by indication (1) "right ventricular (RV) failure," (2) "refractory hypoxemia," and (3) "recurrent suck-down events (SDEs)." Pre- and post-configuration vasoactive inotropic scores (VIS), fraction of inspired oxygen (FIO 2 ), and resolution of SDEs were reported. A 90-day mortality was computed for all groups. Patients were also compared to those who underwent conventional venovenous (VV) ECMO., Results: Forty-seven patients underwent VP ECMO configuration, 18 in group 1, 16 in group 2, and 8 in group 3. Ninety-day mortality was 66% for the entire cohort and was 77.8%, 81.3% and 37.5% for groups 1, 2, and 3, respectively. Mean VIS decreased in group 1 (8.3 vs 2.9, p  = 0.005), while mean FIO 2 decreased in the group 2 and was sustained at 72 h (82.5% vs 52.5% and 47.5%, p  < 0.001). Six of the eight (75%) of patients with recurrent SDEs had resolution of these events after configuration to VP ECMO. Patients with VP ECMO spent more days on ECMO (33 days compared to 18 days, p  = 0.004) with no difference in mortality (66% compared to 55.1%, p  = 0.28)., Conclusion: VP ECMO in COVID-19 ARDS improves hemodynamics in patients with RV failure, improves oxygenation in patients with refractory hypoxemia and improves the frequency of SDEs., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The objective of this study is to clarify the pore structure of ECMO membranes by using our approach and theoretically validate the risk of SARS-CoV-2 permeation. There has not been any direct evidence for SARS-CoV-2 leakage through the membrane in ECMO support for critically ill COVID-19 patients. The precise pore structure of recent membranes was elucidated by direct microscopic observation for the first time. The three types of membranes, polypropylene, polypropylene coated with thin silicone layer, and polymethylpentene (PMP), have unique pore structures, and the pore structures on the inner and outer surfaces of the membranes are completely different anisotropic structures. From these data, the partition coefficients and intramembrane diffusion coefficients of SARS-CoV-2 were quantified using the membrane transport model. Therefore, SARS-CoV-2 may permeate the membrane wall with the plasma filtration flow or wet lung. The risk of SARS-CoV-2 permeation is completely different due to each anisotropic pore structure. We theoretically demonstrate that SARS-CoV-2 is highly likely to permeate the membrane transporting from the patient’s blood to the gas side, and may diffuse from the gas side outlet port of ECMO leading to the extra-circulatory spread of the SARS-CoV-2 (ECMO infection). Development of a new generation of nanoscale membrane confirmation is proposed for next-generation extracorporeal membrane oxygenator and system with long-term durability is envisaged.

In the concept of a biohybrid lung, endothelial cells seeded on gas exchange membranes form a non-thrombogenic an anti-inflammatory surface to overcome the lacking hemocompatibility of today's oxygenators during extracorporeal membrane oxygenation. To evaluate this concept, the long-term stability and gas exchange performance of endothelialized RGD-conjugated polydimethylsiloxane (RGD-PDMS) membranes was evaluated. Human umbilical vein endothelial cells (ECs) were cultured on RGD-PDMS in a model system under physiological wall shear stress (WSS) of 0.5 Pa for up to 33 days. Gas exchange performance was tested with three biological replicates under elevated WSS of 2.5 Pa using porcine blood adjusted to venous values following ISO 7199 and blood gas analysis. EC morphology was assessed by immunocytochemistry (n = 3). RGD-PDMS promoted endothelialization and stability of endothelialized membranes was shown for at least 33 days and for a maximal WSS of 2.5 Pa. Short-term exposure to porcine blood did not affect EC integrity. The gas transfer tests provided evidence for the oxygenation and decarboxylation of the blood across endothelialized membranes with a decrease of transfer rates over time that needs to be addressed in further studies with larger sample sizes. Our results demonstrate the general suitability of RGD-PDMS for biohybrid lung applications, which might enable long-term support of patients with chronic lung failure in the future. [ABSTRACT FROM AUTHOR]

Current artificial lungs fail in 1–4 weeks due to surface-induced thrombosis. Biomaterial coatings may be applied to anticoagulate artificial surfaces, but none have shown marked long-term effectiveness. Poly-carboxybetaine (pCB) coatings have shown promising results in reducing protein and platelet-fouling in vitro. However, in vivo hemocompatibility remains to be investigated. Thus, three different pCB-grafting approaches to artificial lung surfaces were first investigated: 1) graft-to approach using 3,4-dihydroxyphenylalanine (DOPA) conjugated with pCB (DOPA-pCB); 2) graft-from approach using the Activators ReGenerated by Electron Transfer method of atom transfer radical polymerization (ARGET-ATRP); and 3) graft-to approach using pCB randomly copolymerized with hydrophobic moieties. One device coated with each of these methods and one uncoated device were attached in parallel within a veno-venous sheep extracorporeal circuit with no continuous anticoagulation (N = 5 circuits). The DOPA-pCB approach showed the least increase in blood flow resistance and the lowest incidence of device failure over 36-hours. Next, we further investigated the impact of tip-to-tip DOPA-pCB coating in a 4-hour rabbit study with veno-venous micro-artificial lung circuit at a higher activated clotting time of 220–300 s (N ≥ 5). Here, DOPA-pCB reduced fibrin formation (p = 0.06) and gross thrombus formation by 59% (p < 0.05). Therefore, DOPA-pCB is a promising material for improving the anticoagulation of artificial lungs. Chronic lung diseases lead to 168,000 deaths each year in America, but only 2300 lung transplantations happen each year. Hollow fiber membrane oxygenators are clinically used as artificial lungs to provide respiratory support for patients, but their long-term viability is hindered by surface-induced clot formation that leads to premature device failure. Among different coatings investigated for blood-contacting applications, poly-carboxybetaine (pCB) coatings have shown remarkable reduction in protein adsorption in vitro. However, their efficacy in vivo remains unclear. This is the first work that investigates various pCB-coating methods on artificial lung surfaces and their biocompatibility in sheep and rabbit studies. This work highlights the promise of applying pCB coatings on artificial lungs to extend its durability and enable long-term respiratory support for lung disease patients. [ABSTRACT FROM AUTHOR]

The large, densely packed artificial surface area of artificial lungs results in rapid clotting and device failure. Surface generated nitric oxide (NO) can be used to reduce platelet activation and coagulation on gas exchange fibers, while not inducing patient bleeding due to its short half-life in blood. To generate NO, artificial lungs can be manufactured with PDMS hollow fibers embedded with copper nanoparticles (Cu NP) and supplied with an infusion of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP). The SNAP reacts with Cu NP to generate NO. This study investigates clot formation and gas exchange performance of artificial lungs with either NO-generating Cu-PDMS or standard polymethylpentene (PMP) fibers. One miniature artificial lung (MAL) made with 10 wt% Cu-PDMS hollow fibers and one PMP control MAL were attached to sheep in parallel in a veno-venous extracorporeal membrane oxygenation circuit (n = 8). Blood flow through each device was set at 300 mL/min, and each device received a SNAP infusion of 0.12 μmol/min. The ACT was between 110 and 180 s in all cases. Blood flow resistance was calculated as a measure of clot formation on the fiber bundle. Gas exchange experiments comparing the two groups were conducted every 24 h at blood flow rates of 300 and 600 mL/min. Devices were removed once the resistance reached 3x baseline (failure) or following 72 h. All devices were imaged using scanning electron microscopy (SEM) at the inlet, outlet, and middle of the fiber bundle. The Cu-PDMS NO generating MALs had a significantly smaller increase in resistance compared to the control devices. Resistance rose from 26 ± 8 and 23 ± 5 in the control and Cu-PDMS devices, respectively, to 35 ± 8 mmHg/(mL/min) and 72 ± 23 mmHg/(mL/min) at the end of each experiment. The resistance and SEM imaging of fiber surfaces demonstrate lower clot formation on Cu-PDMS fibers. Although not statistically significant, oxygen transfer for the Cu-PDMS MALs was 13.3% less than the control at 600 mL/min blood flow rate. Future in vivo studies with larger Cu–PDMS devices are needed to define gas exchange capabilities and anticoagulant activity over a long-term study at clinically relevant ACTs. In artificial lungs, the large, densely-packed blood contacting surface area of the hollow fiber bundle is critical for gas exchange but also creates rapid, surface-generated clot requiring significant anticoagulation. Monitoring of anticoagulation, thrombosis, and resultant complications has kept permanent respiratory support from becoming a clinical reality. In this study, we use a hollow fiber material that generates nitric oxide (NO) to prevent platelet activation at the blood contacting surface. This material is tested in vivo in a miniature artificial lung and compared against the clinical standard. Results indicated significantly reduced clot formation. Surface-focused anticoagulation like this should reduce complication rates and allow for permanent respiratory support by extending the functional lifespan of artificial lungs and can further be applied to other medical devices. [ABSTRACT FROM AUTHOR]