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Membranoxygenatoren sind medizinische Ger��te, die den Gasaustausch der nat��rlichen Lunge unterst��tzen oder ��bernehmen. Bei modernen Oxygenatoren wird die Gasaustauschfl��che durch Hohlfasermembranpackungen bereitgestellt. W��hrend Blut durch die Mantelseite der Hohlfaserpackung gepumpt wird, wird das Faserlumen mit O2 gesp��lt. CO2 und O2 diffundieren dabei den Partialdruckgradienten folgend durch die Membran. Urspr��nglich wurden Membranoxygenatoren entwickelt, um die Lunge w��hrend eines kardiopulmonalen Bypasses zu ersetzen. Dabei ��bernimmt der Oxygenator den gesamten metabolisch erforderlichen O2- und CO2-Transfer. Mit kontinuierlicher Weiterentwicklung wurden Oxygenatoren als Lungenunterst��tzung bei der Behandlung des akuten Atemnotsyndroms (engl. Acute Respiratory Distress Syndrome, ARDS) eingesetzt. Patienten, die an ARDS leiden, werden h��ufig mit lungenschonender Beatmung (engl. Lung Protective Ventilation, LPV) behandelt. W��hrend die LPV einen ausreichenden O2-Transfer erm��glicht, ist die CO2-Abtrennung begrenzt. Um eine ausreichende CO2-Abtrennung zu gew��hrleisten, werden daher zunehmend Oxygenatoren eingesetzt. Insofern ist es das Ziel dieser Doktorarbeit, eine effizientere Entwicklung von Oxygenator-basierter CO2-Abtrennung zu erm��glichen. Eine effiziente Weiterentwicklung der Oxygenator-basierten CO2-Abtrennung soll dabei auf zwei Arten bewerkstelligt werden. Erstens, durch die Reduktion der Komplexit��t der Versuchskampagnen bei gleichbleibender Verl��sslichkeit der erhobenen Daten. Zweitens, durch die Entwicklung von weniger rechenaufw��ndigen, jedoch pr��zisen Methoden der numerischen Str��mungsmechanik (engl. Computational Fluid Dynamics, CFD). Die Grundlage f��r eine effiziente Entwicklung der CO2-Abtrennung mit Oxygenatoren ist eine exakte Messung der CO2-Abfuhrrate. Im Zuge dieser Arbeit wurden die beiden verf��gbaren Methoden zur Bestimmung der CO2 Abfuhrrate verglichen. Die erste Methode basiert auf Grundlage der Abnahme der CO2-Konzentration im Blut (Blut-basiert). Die zweite Methode basiert auf Grundlage der Zunahme der CO2-Konzentration im Sp��lgas des Oxygenators (Sp��lgas-basiert). Unsere Studie zeigt, dass die Sp��lgas-basierte Methode mit einem Messfehler von 3 % der gemessenen CO2-Abtrennrate besser abschneidet. Dieser Fehler liegt signifikant (p < 0,05) unter dem Messfehler der Blut-basierten Methode (16 % des Messwerts). Au��erdem wurde Wasser als Blutersatz f��r die Bestimmung der CO2-Abtrennrate von Oxygenatoren untersucht. Obwohl Wasser ein g��ngiger Blutersatz ist, um den experimentellen Aufwand und Tierleid zu verringern, wurde dessen Anwendungsgrenze und Zuverl��ssigkeit in der Literatur noch nicht systematisch analysiert. Daher haben wir die CO2-Abfuhrrate von Blut und Wasser bei drei pathologisch erh��hten CO2-Partialdr��cken (50, 70, 100 mmHg) und drei Blutflussraten (1000, 1300, 1600 mL/min) verglichen. Unsere experimentellen Daten zeigen eine durchschnittliche Abweichung von 10 % zwischen der CO2-Abfuhrrate von Blut und Wasser. Die geringe Abweichung kann auf die gegens��tzlichen Einfl��sse der Materialeigenschaften der beiden Fl��ssigkeiten zur��ckgef��hrt werden. Mit Hilfe von CFD-Simulationen konnten wir die verschiedenen Beitr��ge der unterschiedlichen Materialeigenschaften quantifizieren. Die im Vergleich zu Wasser h��here CO2-L��slichkeit von Blut und die damit einhergehende h��here CO2-Abfuhrrate (+ 125 %) wird gr����tenteils durch die geringere CO2-Diffusionsrate von Blut (- 53 %), gefolgt von der bei Blut vorliegenden geringeren CO2-Permeanz (- 18 %) und der h��heren Viskosit��t von Blut (- 10 %) kompensiert. W��hrend dies zu richtigen makroskopischen CO2-Abfuhrraten f��hrt, konnten wir zeigen, dass die aufgebaute Grenzschicht ��� der gr����te CO2-Transportwiderstand in Oxygenatoren ��� sich zwischen Blut und Wasser grundlegend unterscheidet. Die beiden Fl��ssigkeiten folgen insofern nicht der gleichen dimensionslosen Massentransportkorrelation. Daher sollte die Verwendung von Wasser als Blutmodell auf die makroskopische Bestimmung der CO2-Abfuhrrate beschr��nkt sein und nicht f��r Untersuchungen der Grenzschicht verwendet werden. Neben Wasser als CO2-Transportmodell wurden in dieser Arbeit zudem auch w��ssrige L��sungen und Tierblut als rheologische Modelle f��r Blut untersucht. W��hrend experimentelle Daten am zuverl��ssigsten sind, beschr��nken sie sich meist auf punktuelle Werte an leicht zug��nglichen Stellen. CFD Simulationen k��nnen diese Daten erweitern, sind jedoch aufgrund des feinen Rechengitters, das zur Aufl��sung des diffusiven CO2-Transports in der Membranpackung erforderlich ist, numerisch aufwendig. Daher ist in der aktuellen Literatur eine L��cke zwischen den geometrischen Gr����enskalen von Stofftransportsimualtionen und hydrodynamischen Simulationen von Oxygenatormembranpackungen zu verzeichnen. Um diese L��cke zu schlie��en, wurde eine Up-Scaling-Methode entwickelt. Sie erm��glicht es, den transmembranen Transport, der auf Basis von Stofftransportsimulationen einer reduzierten Geometrie berechnet wurde, auf die geometrischen Gr����enskalen von hydrodynamischen Str��mungssimulationen zu skalieren. Die durchschnittliche Abweichung zwischen experimentell ermittelter und durch die Up-Scaling-Methode numerisch vorhergesagter CO2-Abfuhrrate eines Prototyp-Oxygenators betr��gt im Mittel 6 % f��r Blut und 3 % f��r Wasser. Als weitere Besonderheit ist unser CFD-Modell in der Lage, den CO2-Transport in der Membranwand und dem Faserlumen aufzul��sen. W��hrend der Membranwandwiderstand in der Literatur oft als vernachl��ssigbar angesehen wird, konnten wir zeigen, dass die Permeanz aufgrund des Eindringens von Blutplasma auf 22 % ihres urspr��nglichen Wertes sinken kann. CFD-Simulationen zeigen, dass dies zu einer direkt proportionalen Abnahme der CO2-Abfuhrrate f��hren w��rde. Um eine hohe Genauigkeit eines CFD-Modells zu gew��hrleisten, sind au��erdem geeignete Modelle f��r die komplexen Materialeigenschaften von Blut erforderlich. Im Rahmen dieser Arbeit wurden zwei der relevantesten Materialeigenschaften, die CO2-L��slichkeit und die Viskosit��t des Blutes untersucht. Auf der Grundlage unserer Daten k��nnen wir ein einfaches und zuverl��ssiges CO2-L��slichkeitsmodell empfehlen. Dar��ber hinaus wurden Viskosit��tsmodelle f��r Schaf-, Rinder-, Pferde- und Schweineblut in Abh��ngigkeit von der Scherrate, dem H��matokrit und der Temperatur entwickelt. Abschlie��end wurde ein CFD-Modell mit reduzierter Komplexit��t, das auf der Berechnung lokaler Sherwood-Zahlen basiert, erfolgreich getestet. Es erlaubte den Einsatz von mikrostrukturierten Hohlfasermembranen in Oxygenatormembranpackungen hinsichtlich des CO2-Transportwiderstandes im Blut qualitativ zu bewerten. Fazit: Die in dieser Dissertation durchgef��hrten Arbeiten stellen eine solide Grundlage f��r die Planung von experimentellen und numerischen Untersuchungen der CO2-Abtrennleistung von Oxygenatoren dar. Basierend auf den experimentellen Erkenntnissen sowie den Fortschritten in der CFD-Modellierung kann in Zukunft eine erfolgreiche und effiziente Entwicklung der Oxygenator-basierten CO2-Abtrennung erreicht werden., Membrane oxygenators are medical devices used to support or take over the gas exchange of the natural lung. In modern oxygenators, the gas exchange surface is provided by a hollow fiber membrane packing. While blood is pumped through the shell side of the hollow fiber packing, O2 is used to sweep the fiber lumen. CO2 and O2 are exchanged through the membrane following the partial pressure gradient. Consequently, blood is enriched with O2 and purged from CO2. Initially, membrane oxygenators were developed to supplement the natural lung during cardiopulmonary bypass. Here, the oxygenator has to take over the total metabolically required O2 and CO2 transfer. With continuous development, oxygenators were applied as lung support to manage acute respiratory distress syndrome (ARDS). Patients suffering from ARDS are often treated with lung protective ventilation (LPV). While LPV allows sufficient O2 transfer, the CO2 removal is limited. The limited CO2 removal evokes serious side effects such as upcoming hypercapnia and hypercapnic acidosis. Consequently, oxygenators are increasingly used to provide additional CO2 removal during LPV to circumvent the mentioned side effects. This doctoral research aims to improve the development process of oxygenator-based CO2 removal. A particular focus is placed on the initial development phase, where the work is strongly characterized by engineering challenges such as design, assembly, and first basic performance tests. The development process shall be improved in two ways. First, by designing experimental campaigns that are simple, inexpensive, and reliable. Second, by developing numerically inexpensive and accurate computational fluid dynamic (CFD) methods for in-depth insights into the CO2 separation process. The fundament for efficient development of oxygenator-based CO2 removal is an accurate measurement of the CO2 removal rate. We compared the two available CO2 removal rate determination methods, i.e., the determination based on CO2 concentration decrease in the blood (blood-based) and the determination based on CO2 concentration increase in the sweep flow (sweep flow-based). Our study shows that the sweep flow-based method performed superior with a CO2 removal measurement error of 3 % of reading. This error lies significantly (p < 0.05) under the CO2 removal measurement error of the blood-based method (16 % of reading). Furthermore, blood mimicking fluids for the determination of the CO2 removal rate of oxygenators were evaluated. While water tests are a common method to reduce experimental effort and avoid animal tests, its application limits and reliability have never been analyzed systematically in the literature. Consequently, we compared the CO2 removal rate of blood and water at three pathological elevated CO2 partial pressures (50, 70, 100 mmHg) and three blood flow rates commonly applied in blood oxygenation (1000, 1300, 1600 mL/min). Our experimental data shows an average 10 % deviation between the CO2 removal rate of blood and water. The low deviation can be attributed to the opposing influences of the material properties of the two liquids. Using CFD simulations, we could quantify the contributions of the different material properties. Compared to water, the higher CO2 solubility of blood and the accompanied increased CO2 removal rate (+ 125 %) is in most parts compensated by the lower CO2 diffusion rate of blood (- 53 %), followed by the lower CO2 permeance available with blood (- 18 %) and the higher viscosity of blood (- 10 %). While this leads to comparable macroscopic CO2 removal rates, we could elaborate that the boundary layer built up ��� the main CO2 transport resistance in oxygenators ��� is fundamentally different between blood and water, i.e., the two liquids do not follow the same dimensionless mass transport analogy. Hence the use of water as a blood model should be limited to the macroscopic determination of the CO2 removal rate and not be used in studies of the boundary layer. In addition to water as a CO2 transport model, this work investigated aqueous and animal blood models as rheological models for blood. While experimental data is most reliable, it is mainly limited to pointwise data at easily accessible locations. Computational fluid dynamic (CFD) simulations can extend this data. However, they are numerically expensive due to the highly refined computational mesh required to resolve the diffusive CO2 transport in the membrane packing. Consequently, in the current literature, a gap between the geometric size scales of mass transfer and hydrodynamic simulations of oxygenator membrane packings can be recorded. In order to bridge this gap, an up-scaling method was developed. It allows scaling the transmembrane transport predicted in species transport simulations of a reduced geometry on the geometrical scales of flow simulations. This is done by calculating velocity inlet conditions of the reduced geometry based on the average velocity within the complete packing determined via CFD flow simulations. By doing so, the flow distribution in the reduced geometry is representative of the flow regime within the complete packing. This was proven by comparing experimental and numerical results. The deviation between the experimentally determined and numerically predicted CO2 removal rate of a prototype oxygenator amounts on average to 6 % for blood and 3 % for water. As a further novelty, our CFD model for the species transport in blood oxygenators can resolve the CO2 transport in the membrane wall and the fiber lumen. While the membrane wall resistance is often considered negligible in literature, we could show that membrane permeance can reduce to 22 % of its original value due to plasma leakage or pervaporation. CFD simulations show that this would result in a proportional decrease of the CO2 removal rate. This is important since numerical overprediction of the CO2 removal rate poses a risk of incorrect validation of CFD models. In order to guarantee high accuracy of a CFD model, suitable models for the complex material properties of blood are required. In the scope of this work, models for two of the most relevant material properties in oxygenator-based CO2 removal, CO2 solubility of blood and viscosity of blood, were investigated. Based on our data, we can recommend a simple and reliable CO2 solubility model proposed in the literature. Furthermore, viscosity models for ovine, bovine, equine, and porcine blood are presented as a function of shear rate, hematocrit, and temperature. Finally, a less complex CFD model based on the calculation of local Sherwood numbers was successfully tested. It allows to qualitatively assess different microstructures of hollow fiber membranes regarding their CO2 transport resistance in blood. To conclude, the research conducted in this doctoral thesis offers a solid foundation for designing reliable experimental and numerical investigations of oxygenator-based CO2 removal. Due to the experimental findings and advances in CFD modeling, oxygenator-based CO2 removal can be efficiently developed in the future.

Since the beginning of 2020, the entire world has been affected by Covid-19, which has caused millions of infections and deaths, with older adults being the most affected population. Like many other countries in the world, Ecuador has shown a deficit of supplies to face this threat. Within this context, this article shows a pressure-cycled artificial ventilator alternative constructed with 3D printing material. The procedure includes a structural analysis simulation, the topology optimization of the mechanical structure and the implementation of air pressure control in the artificial lung bag. The results of this research shows that the proposed structural design for the artificial ventilator allows reducing the amount of construction material and therefore the manufacturing time, without affecting the effectiveness of its performance. In addition, analysis of the control system responses evidences that a classical PID controller allows the correct performance of the ventilator pressure control.

EDAC is defined by an abnormal expiratory reduction of the tracheal lumen leading to an elevation of airflow resistance. No data supports the clinical threshold of 50% closure. The aim of our study was to develop an experimental model of EDAC in order to assess the consequences of airway collapse on the work of breathing (WOB) and evaluate the impact of CPAP. We have modelled and manufactured a realistic 3D silicon trachea and a static compression system to simulate tracheal collapse. The trachea was linked to a dummy head with realistic upper airways and to an artificial lung (ASL 5000, IngMar Medical) which simulated tidal breathing (TB) from three lung models (normal, COPD and restrictive). We simulated tracheal compressions (length 4 or 8 centimeters, closure of 0,31,49,63 and 87%) at rest and on exercise, without and with CPAP (PEP 5, 10, 15 and 20cmH2O). We measured pressure on both sides of collapse and computed expiratory resistance Rexp, flow Qexp and pressure time product (PTPexp which reflects WOB). There was a significant impact of the degree of collapse on Rexp, Qexp and PTPexp for a closure ≥49%. During TB, median Rexp was 8,05 [6,60;9,90]cmH2O.s/L at 87% collapse versus 0,12 [0,11;0,14]cmH2O.s/L without collapse (p Our experimental model supports the 49% closure threshold associated with significant consequences on WOB.

Background 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. Methods 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 NO2 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-N2O2) 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. Results 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. Conclusions 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.

Annotation. The use of artificial lung ventilation in patients of intensive care unit often leads to airway contamination of conditionally pathogenic microorganisms and the development of ventilator-associated pneumonia. The clinical manifestations of ventilator-associated pneumonia can vary widely from mild to development of critical conditions accompanied by septic shock. This significantly worsens the patient's condition and prognosis for effective treatment. The paper presents the results of the study of the use of adhesive antiseptic compositions based on the domestic antiseptic drug decamethoxin in order to give antimicrobial properties to intubation tubes. An antibacterial adhesive was applied to the surface of segments of the endotracheal intubation tube, after which the samples were dried in a sterile box. The sensitivity of the microorganisms to the components of the antiseptic compositions was studied by the diameter of the growth retardation zone around the studied fragments of endotracheal intubation tubes placed in the thickness of the pre-seeded microorganism’s dense nutrient medium. The results were statistically analyzed using standard application package for biomedical research “STATISTICA 5.5”. It has been proved that adhesive film-forming compositions based on decamethoxin confer pronounced antimicrobial properties to endotracheal intubation tubes. The most susceptible to antimicrobial activity were gram-positive microorganisms of the genus Staphylococcus, and the most resistant were representatives of gram-negative bacteria of the genus Acinetobacter. The obtained research results allow us to predict the effectiveness of the use of adhesive hydrophilic and hydrophobic antiseptic compositions based on the domestic antiseptic decamethoxin to provide protective properties of the surface of endotracheal tubes, prevent the process of bacterial film formation and prevention of ventilator-associated patients.

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 Auto-Regulatory 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 (SpO(2) = 96.3 % ± 4.29, pH = 7.44 ± 0.09, pCO(2) = 38.9 ± 9.9 mmHg, and pO(2) =237.9 ± 123.6 mmHg) during simulated respiratory distress. Acceptable correlation between oxygenator exhaust gas CO(2) and oxygenator outlet pCO(2) were observed (R(2)= 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.

Wearable extracorporeal membrane oxygenation (ECMO) circuits may soon become a viable alternative to conventional ECMO treatment. Common device-induced complications, however, such as blood trauma and oxygenator thrombosis, must first be addressed to improve long-term reliability, since ambulatory patients cannot be monitored as closely as intensive care patients. Additionally, an efficient use of the membrane surface can reduce the size of the devices, priming volume, and weight to achieve portability. Both challenges are linked to the hemodynamics in the fiber bundle. While experimental test methods can often only provide global and time-averaged information, computational fluid dynamics (CFD) can give insight into local flow dynamics and gas transfer before building the first laboratory prototype. In this study, we applied our previously introduced micro-scale CFD model to the full fiber bundle of a small oxygenator for gas transfer prediction. Three randomized geometries as well as a staggered and in-line configuration were modeled and simulated with Ansys CFX. Three small laboratory oxygenator prototypes were built by stacking fiber segments unidirectionally with spacers between consecutive segments. The devices were tested in vitro for gas transfer with porcine blood in accordance with ISO 7199. The error of the predicted averaged CFD oxygen saturations of the random 1, 2, and 3 configurations relative to the averaged in-vitro data (over all samples and devices) was 2.4%, 4.6%, 3.1%, and 3.0% for blood flow rates of 100, 200, 300, and 400 ml/min, respectively. While our micro-scale CFD model was successfully applied to a small oxygenator with unidirectional fibers, the application to clinically relevant oxygenators will remain challenging due to the complex flow distribution in the fiber bundle and high computational costs. However, we will outline our future research priorities and discuss how an extended mass transfer correlation model implemented into CFD might enable an a priori prediction of gas transfer in full size oxygenators.

Although lung transplantation can be used to treat lung failure, limited donor organ availability creates a pressing need for improved artificial lung technology. This review discusses recent developments and future research pathways for respiratory assist devices and regenerative therapies intended to treat advanced lung disease. Hollow fiber membrane gas exchangers can be used to bridge lung failure patients to transplantation. Engineering improvements to such devices are on the verge of enabling longer term wearable systems that simplify and improve support. Progress with microchannel-based devices provides hope of smaller, more biomimetic devices that may even enable implantation; however, further development and testing are needed. Advances in cell-based technologies and tissue engineering have enabled early proof of concept of bioartificial lungs with properties similar to the native organ. Recent progress with artificial lungs has enabled better treatment as a bridge therapy. Continued advances in both engineering and biology will be necessary to achieve a truly implantable artificial lung capable of destination therapy.

Objective. To identify risk factors for acute cardiac surgery-associated kidney damage in 214 newborns and infants with congenital heart defects. Results. 54.7% of 95 newborns and 46.2% of 119 infants have acute cardiac surgery-associated kidney injury. There have been determined statistically significant risk factors of acute cardiac surgery-associated kidney injury: in newborns – the level of lactate in blood plasma more than 2.5 mmol/l and artificial lung ventilation (87.1% as compared to 39.1% without these factors; 93.8 and 46.8% accordingly; р<0.001), in infants – level of lactate in blood plasma more than 2.5 mmol/l before surgery as compared to those without these factors (96.4% as compared to 30.8% without this factor; р<0.001).

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.

The article describes the successful experience of treating a female patient with severe poisoning by a mixture of drugs with a predominant cardiotoxic effect. The number of drugs taken was many times higher than the potentially lethal dose. Hemodynamics has been supported by vasopressors and inotropic drugs for a long time, antidotes, sorbents, detoxification agents were used. Due to inadequate spontaneous ventilation, the patient was on artificial lung ventilation for 24 days. After 26 days in the intensive care unit, she was transferred to the therapeutic department in a stable state and without neurological deficit. We believe that this material will be useful for intensive care physicians when providing emergency care to patients in such situations., Стаття присвячена успішному досвіду лікування пацієнтки з тяжким отруєнням сумішшю медикаментів з переважною кардіотоксичною дією. Кількість вжитих препаратів багатократно перевищувала потенційно смертельну дозу. Гемодинаміка тривалий час підтримувалася вазопресорами та препаратами інотропної дії, застосовувалися антидоти, сорбенти, дезінтоксикаційні середники. У зв’язку з неадекватною спонтанною вентиляцією 24 дні пацієнтка перебувала на штучній вентиляції легень. Через 26 діб перебування у відділенні інтенсивної терапії переведена до терапевтичного відділення у стабільному стані та без неврологічного дефіциту. Вважаємо, що цей матеріал буде корисним для лікарів відділень інтенсивної терапії при наданні невідкладної допомоги хворим у подібних ситуаціях.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can spread through virus-containing aerosols ( ≤ 5 μm) and larger airborne droplets. Quantifying filtration efficiency of different kinds of masks and linings for aerosols that fall within the most penetrating particle size (80-400 nm) is critical to limiting viral transmission. The objective of our experiment was to compare the “real-world” filtering efficiency of different face masks for fine aerosols (350 nm) in laboratory simulations.Methods: We performed a simulated bench test that measured the filtering efficiency of N95 vs. N99 masks with elastomeric lining in relation to baseline (“background”) aerosol generation. A mannequin head was placed within a chamber and was attached to an artificial lung simulator. Particles of known size (350 ± 6 nm aerodynamic diameter) were aerosolized into the chamber while simulating breathing at physiological settings of tidal volume, respiratory rate, and airflow. Particle counts were measured between the mannequin head and the lung simulator at the tracheal airway location.Results: Baseline particle counts without a filter (background) were 2,935 ± 555 (SD) cm−3, while the N95 (1348 ± 92 cm−3) and N99 mask with elastomeric lining (279 ± 164 cm−3; p Conclusion: The filtration efficiency of the N95 (54.1%) and N99 (90.5%) masks were lower than the filtration efficiency rating. N99 masks with elastomeric lining exhibit greater filtration efficiency than N95 masks without elastomeric lining and may be preferred to contain the spread of SARS-CoV-2 infection.

BackgroundNebulizers are medical devices that deliver aerosolized medication directly to lungs to treat a variety of respiratory diseases. However, breathing patterns, respiration rates, airway diameters, and amounts of drugs delivered by nebulizers may be respiratory disease dependent.MethodIn this study, we developed a respiratory simulator consisting of an airway model, an artificial lung, a flow sensor, and an aerosol collecting filter. Various breathing patterns were generated using a linear actuator and an air cylinder. We tested six home nebulizers (jet (2), static (2), and vibrating mesh nebulizers (2)). Nebulizers were evaluated under two conditions, that is, for the duration of nebulization and at a constant output 1.3 mL using four breathing patterns, namely, the breathing pattern specified in ISO 27427:2013, normal adult, asthmatic, and COPD.ResultsOne of the vibrating mesh nebulizers had the highest dose delivery efficiency. The drug delivery efficiencies of nebulizers were found to depend on breathing patterns.ConclusionWe suggest a quantitative drug delivery efficiency evaluation method and calculation parameters that include considerations of constant outputs and residual volumes. The study shows output rates and breathing patterns should be considered when the drug delivery efficiencies of nebulizers are evaluated.

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, and microfluidic oxygenators are outlined.

Optimizing patient care based on precision oncology will inevitably become the standard of care. If we accept the principle that every persons’ cancer is different then the most effective therapies will have to be designed for the individual patient and for their tumors genetic profile. Access to tumor mutational profiling is now widely available but continues to be limited by cost and actionable information. For example, novel combinations of approved drugs are rarely considered. These considerations lead us to hypothesize that artificially induced Lung Adenocarcinoma (LUAD) derived lung organoids could provide a novel, alternate approach for LUAD disease modeling and large-scale targeted drug screening.In this project, we used data from a commercially available tumor mutation profile to generate and then validate the artificially induced LUAD-derived lung organoid simulations (aiLUNG-LUAD) to model LUAD and identify several drug combinations that effectively reverse the tumors’ genotypic and phenotypic features when compared with placebo. These results complement previous LUAD-derived lung organoids research and provide a novel and widely applicable cancer drug-screening approach for precision/individualized oncology.

Introduction: An important phase in surgical training is gaining experience in real human anatomical situations. When a cadaver is available it may complement the various artificial practice models. However, it is often necessary to supplement the characteristics of the cadavers with a simulation of a tumor. Our objective was to develop an easy-to-create, realistic artificial tumor-mimic model for peripheral lung tumor resection practice.Methods: In our work we injected barium sulphate enriched silicone suspension into 10 isolated, non-fixed lungs of human cadavers, through the puncture of the visceral pleura. Four lesions–apical, hilar and two peripheral–were created in each of ten specimens. After fixation CT scans were obtained and analyzed. The implanted tumor-mimics were examined after anatomical preparation and slicing. Also performed CT-guided percutaneous puncture was also performed to create the lesions in situ in two lungs of human cadavers.Results: Analyzing the CT data of 10 isolated lungs, out of 40 lesions, 34 were nodular (85.0%) and in the nodular group five were spiculated (12.5%). Satellite lesions were formed in two cases (5.0%). Relevant outflow into vessels or airway occurred in five lesions (12.5%). Reaching the surface of the lung occured in 11 lesions (27.5%). The tumor-mimics were elastic and adhered well to the surrounding tissue. The two lesions, implanted via percutaneous puncture, both were nodular and one also showed lobulated features.Conclusion: Our artificial tumor-mimics were easy to create, varied in shape and size, and with percutaneous implantation the lesions provide a model for teaching every step of a surgical procedure.

While previous in vitro studies showed divergent results concerning the influence of pulsatile blood flow on oxygen advection in oxygenators, no study was done to investigate the uncertainty affected by blood flow dynamics. The aim of this study is to utilize a computational fluid dynamics model to clarify the debate concerning the influence of pulsatile blood flow on the oxygen transport. The computer model is based on a validated 2D finite volume approach that predicts oxygen transfer in pulsatile blood flow passing through a 300-micron hollow-fiber membrane bundle with a length of 254 mm, a building block for an artificial lung device. In this study, the flow parameters include the steady Reynolds number (Re = 2, 5, 10 and 20), Womersley parameter (Wo = 0.29, 0.38 and 0.53) and sinusoidal amplitude (A = 0.25, 0.5 and 0.75). Specifically, the computer model is extended to verify, for the first time, the previously measured O2 transport that was observed to be hindered by pulsating flow in the Biolung, developed by Michigan Critical Care Consultants. A comprehensive analysis is carried out on computed profiles and fields of oxygen partial pressure (PO2) and oxygen saturation (SO2) as a function of Re, Wo and A. Based on the present results, we observe the positive and negative effects of pulsatile flow on PO2 at different blood flow rates. Besides, the SO2 variation is not much influenced by the pulsatile flow conditions investigated. While being consistent with a recent experimental study, the computed O2 volume flow rate is found to be increased at high blood flow rates operated with low frequency and high amplitude. Furthermore, the present study qualitatively explains that divergent outcomes reported in previous in vitro experimental studies could be owing to the different blood flow rates adopted. Finally, the contour analysis reveals how the spatial distributions of PO2 and SO2 vary over time.

Herein we describe the modular design and manufacturing of an emergency ventilator based on cyclical compression of a resuscitation bag to face the COVID-19 pandemic. This was done to mitigate the staggering conditions to supply these medical devices under challenging scenarios of need and logistics. The design is based on international standards and commissions for medical electrical equipment, particular requirements for basic safety, electromagnetic compatibility, and essential performance of critical care and emergency ventilators. The modular design is capable of providing four ventilation modes: volume/pressure mandatory ventilation and volume/pressure assisted ventilation. After testing with artificial lungs, calibration, and validation instruments it was found that the main ventilation parameters achieved are: maximum tidal volume of 700 mL, maximum pressure of 50 cmH2O, inspiration/expiration ratio up to 1:4 at 30 breaths per minute. The MEDIIK designation is derived from the mayan word ik’ which means wind.

Ventilator shortages occurred due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This in vitro study evaluated the effectiveness of 3-dimensional (3D)-printed splitters and 3D-printed air flow limiters (AFL) in delivering appropriate tidal volumes (TV) to lungs with different compliances. Groups were divided according to the size of the AFL: AFL-4 was a 4-mm device, AFL-5 a 5-mm device, AFL-6 a 6-mm device, and no limiter (control). A ventilator was split to supply TV to 2 artificial lungs with different compliances. The AFL improved TV distribution.

In COVID-19 therapy with artificial lungs such as extracorporeal membrane oxygenation (ECMO) machines, platelets in the extracorporeal circulation are often activated by their contact with the artificial materials, leading to the formation of blood clots followed by serious complications such as stroke and heart attack. However, anticoagulation and antithrombotic management is challenging due to the lack of testing tools to evaluate the circulation. Here we demonstrate real-time monitoring of thrombogenesis in the circulation of an ECMO-equipped goat with an intelligent platelet aggregate characterizer (iPAC), which is based on imaging flow cytometry and deep-learning-based analysis of numerous platelet aggregates in blood.

We demonstrate Endoscopic Optical Coherence Elastography (Endo-OCE) imaging of bronchus in an artificial breathing lung model that can breathe at 10 times per minute with a tidal volume of 500 ml. A 1.2 mm motorized catheter was delivered to the distal bronchus via the working channel of a clinical bronchoscope. Endo-OCE images was acquired at 3000 frames/s during the exhalation of the "breath". The results show that the passive breathing of the lung model can induce sufficient tissue deformation (strain) for Endo-OCE imaging. The lung model can be a useful tool to validate the Endo-OCE technology.

IntroductionThe COVID-19 pandemic has revealed an immense, unmet and international need for available ventilators. Both clinical and engineering groups around the globe have responded through the development of “homemade” or do-it-yourself (DIY) ventilators. Several designs have been prototyped, tested, and shared over the internet. However, many open source DIY ventilators require extensive familiarity with microcontroller programming and electronics assembly, which many healthcare providers may lack. In light of this, we designed and bench tested a low-cost, pressure-controlled mechanical ventilator that is “plug and play” by design, where no end-user microcontroller programming is required. This Fast-AssembLy COVID-Nineteen (FALCON) emergency prototype ventilator can be rapidly assembled and could be readily modified and improved upon to potentially provide a ventilatory option when no other is present, especially in low- and middle-income countries.HypothesisWe anticipated that a minimal component prototype ventilator could be easily assembled that could reproduce pressure/flow waveforms and tidal volumes similar to a hospital grade ventilator (Engström CarestationTM).Materials and MethodsWe benched-tested our prototype ventilator using an artificial test lung under 36 test conditions with varying respiratory rates, peak inspiratory pressures (PIP), positive end expiratory pressures (PEEP), and artificial lung compliances. Pressure and flow waveforms were recorded, and tidal volumes calculated with prototype ventilator performance compared to a hospital-grade ventilator (Engström CarestationTM) under identical test conditions.ResultsPressure and flow waveforms produced by the prototype ventilator were highly similar to the CarestationTM. The ventilator generated consistent PIP/PEEP, with tidal volume ranges similar to the CarestationTM. The FALCON prototype was tested continuously for a 5-day period without failure or significant changes in delivered PIP/PEEP.ConclusionThe FALCON prototype ventilator is an inexpensive and easily-assembled “plug and play” emergency ventilator design. The FALCON ventilator is currently a non-certified prototype that, following further appropriate validation and testing, might eventually be used as a life-saving emergency device in extraordinary circumstances when more sophisticated forms of ventilation are unavailable.

We consider the problem of controlling an invasive mechanical ventilator for pressure-controlled ventilation: a controller must let air in and out of a sedated patient’s lungs according to a trajectory of airway pressures specified by a clinician.Hand-tuned PID controllers and similar variants have comprised the industry standard for decades, yet can behave poorly by over- or under-shooting their target or oscillating rapidly.We consider a data-driven machine learning approach: First, we train a simulator based on data we collect from an artificial lung. Then, we train deep neural network controllers on these simulators. We show that our controllers are able to track target pressure waveforms significantly better than PID controllers.We further show that a learned controller generalizes across lungs with varying characteristics much more readily than PID controllers do.

The recent outbreak of the COVID-19 pandemic in 2020 reasserted the necessity of artificial lung membrane technology to treat patients with acute lung failure. In addition, the aging world population inevitably leads to higher demand for better artificial organ (AO) devices. Membrane technology is the central component in many of the AO devices including lung, kidney, liver and pancreas. Although AO technology has improved significantly in the past few decades, the quality of life of organ failure patients is still poor and the technology must be improved further. Most of the current AO literature focuses on the treatment and the clinical use of AO, while the research on the membrane development aspect of AO is relatively scarce. One of the speculated reasons is the wide interdisciplinary spectrum of AO technology, ranging from biotechnology to polymer chemistry and process engineering. In this review, in order to facilitate the membrane aspects of the AO research, the roles of membrane technology in the AO devices, along with the current challenges, are summarized. This review shows that there is a clear need for better membranes in terms of biocompatibility, permselectivity, module design, and process configuration.

COVID-19 is a disease caused by the SARS-CoV virus. It stands for severe acute respiratory syndrome, which affects the lungs. The process of replication and progression of the COVID-19 virus causes the formation of an excessive amount of reactive oxygen species and inflammation. Many studies have been carried out that have demonstrated that hydrogen has strong anti-inflammatory properties. It reduces hypotension and other symptoms by reducing inflammation and oxidative stress. Oxygen mixture, enriched with Hydrogen, - helps to reduce the resistance of the respiratory tract and frees up access to the pulmonary alveolus, which improves the penetration of oxygen into the lungs. Since hydrogen is an antioxidant, it helps to reduce the burden on the immune system, helps to maintain the body's health and its ability to quickly recover. When electrolysers are used to produce an oxygen-hydrogen mixture, alkaline mist and other impurities can enter the patient's lungs and cause poisoning and chemical burns. For this reason, the use of atomic hydrogen obtained from metal hydride sources for ventilation of the lungs will be more effective for treating COVID-19 than a molecular hydrogen-oxygen mixture from an electrolyzer. A functional diagram of a metal hydride source of atomic hydrogen to an artificial lung ventilator is shown. It is possible to create a series of hydrogen storage tanks of various capacities.

Whole-body plethysmography (WBP) is an established method to determine physiological parameters and pathophysiological alteration of breathing in animals and animal models of a variety of diseases, reaching from pulmonary diseases to complex neurological syndromes. Although frequently used, there is ongoing debate about what exactly is measured by whole-body-plethysmography and how reliable the data derived from this method are? Here, we designed a simple device that can serve as an artificial lung model that enables a thorough evaluation of different predictions about and around whole-body plethysmography. Using our lung model, we confirmed that during WBP two components contribute to the pressure changes detected in the chamber: 1) the increase of the pressure due to heating and moistening of the air, termed as conditioning, during inspiration; 2) changes of chamber pressure that depend on airway resistance. Both components overlap and contribute to the temporal pressure-profile measured in the chamber or across the wall of the chamber. Our data showed that a precise measurement of the breathing volume appears to be hindered by at least two factors: 1) the unknown relative contribution of each of these components; 2) not only the air in the inspired volume is conditioned during inspiration, but also air within the residual volume and death space that is recruited during inspiration. Moreover, our data suggest that the expiratory negative pressure peak that is used to determine the so called “enhanced pause” (Penh) parameter is not a measure for airway resistance as such but rather a consequence of the animal’s response to the airway resistance, using active expiration to overcome the resistance by a higher thoracic pressure.

Background: For children with severe lung disease that cannot wean from ECMO, an implantable artificial lung would permit extubation and support gradual lung recovery from acute disease or provide a bridge to transplantation. We evaluate the function of the novel Pediatric MLung—an efficient, implantable, pumpless artificial lung developed specifically for children—in healthy animal subjects. Methods: Adolescent “mini sheep” weighing 12-20 …

The paper deals with development of an artificial lung ventilation. The aim of the paper is to present developed ventilator based on bag-valve-mask, which could be used as alternative to mechanical ventilator in critical situations related to COVID-19. At first, we present basic principles of positive pressure ventilation. Subsequently, we introduce a requirements to emergency mechanical ventilator in order to be suitable alternative in hospitals as well as in households. The mechanical and control design are presented in the next section. Finally, we experimentally verify developed ventilator with focus on measured pressure of patient airways. The presented results show a potential of developed ventilator to be used at practical level.

Artificial lung (AL) membranes are used for blood oxygenation for patients undergoing open-heart surgery or acute lung failures. Current AL technology employs polypropylene and polymethylpentene membranes. Although effective, these membranes suffer from low biocompatibility, leading to undesired blood coagulation and hemolysis over a long term. In this work, we propose a new generation of AL membranes based on amphiphobic fluoropolymers. We employed poly(vinylidene-co-hexafluoropropylene), or PVDF-co-HFP, to fabricate macrovoid-free membranes with an optimal pore size range of 30-50 nm. The phase inversion behavior of PVDF-co-HFP was investigated in detail for structural optimization. To improve the wetting stability of the membranes, the fabricated membranes were coated using Hyflon AD60X, a type of fluoropolymer with an extremely low surface energy. Hyflon-coated materials displayed very low protein adsorption and a high contact angle for both water and blood. In the hydrophobic spectrum, the data showed an inverse relationship between the surface free energy and protein adsorption, suggesting an appropriate direction with respect to biocompatibility for AL research. The blood oxygenation performance was assessed using animal sheep blood, and the fabricated fluoropolymer membranes showed competitive performance to that of commercial polyolefin membranes without any detectable hemolysis. The data also confirmed that the bottleneck in the blood oxygenation performance was not the membrane permeance but rather the rate of mass transfer in the blood phase, highlighting the importance of efficient module design.

Left ventricular assist devices (LVADs) are increasingly used as destination therapy or as a bridge to future cardiac transplant in patients with end-stage heart failure. Extracorporeal membrane oxygenation (ECMO) can be used to bridge patients in cardiogenic shock or with decompensated heart failure to durable mechanical circulatory support. We assessed outcomes in patients in critical cardiogenic shock (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1) who underwent implantation of a continuous-flow (CF)-LVAD, with or without preoperative ECMO bridging. For this retrospective study, we selected INTERMACS profile 1 patients who underwent CF-LVAD implantation at our institution between Sep 1, 2004 and Nov 30, 2018. Of 768 patients identified, 133 (17.3%) were INTERMACS profile 1; 26 (19.5%) received preoperative ECMO support, and 107 (80.5%) did not. Postimplantation outcomes were compared between the ECMO and no-ECMO groups. No significant differences were found in 30-day mortality (15.4 vs. 15.9%, P = 0.95) or survival at 1 year (53.8 vs. 60.9%, P = 0.51). Three patients who received ECMO before CF-LVAD implantation subsequently underwent cardiac transplant. In the ECMO group, the lactate level 1 day after ECMO initiation was lower in survivors than nonsurvivors (2.7 ± 2.2 vs. 7.4 ± 4.2 mmol/L, P = 0.02; area under the curve = 0.85, P = 0.01) after CF-LVAD implantation. Bridging with ECMO to CF-LVAD implantation in carefully selected INTERMACS profile 1 patients (those who are at the highest risk for critical cardiogenic shock and for whom palliation may be the only other option) produced acceptable postoperative outcomes. Field of research: Artificial lung/ECMO.

Measurements of transcutaneous carbon dioxide (tcCO2) have been used in multiple venues, such as during procedures utilizing jet ventilation, hyperbaric oxygen therapy, as well as both the adult and neo-natal ICUs. However, tcCO2 measurements have not been validated under conditions which utilize an artificial lung, such cardiopulmonary bypass (CPB). The purpose of this study was to (1) validate the use of tcCO2 using an artificial lung during CPB and (2) identify a location for the sensor that would optimize estimation of PaCO2 when compared to the gold standard of blood gas analysis. tcCO2 measurements ( N = 185) were collected every 30 min during 54 pulsatile CPB procedures. The agreement/differences between the tcCO2 and the PaCO2 were compared by three sensor locations. Compared to the earlobe or the forehead, the submandibular PtcCO2 values agreed best with the PaCO2 and with a median difference of –.03 mmHg (IQR = 5.4, p 2 measurement. The multiple linear regression model for predicting the agreement between the submandibular tcCO2 and PaCO2 included the SvO2, the oxygenator gas to blood flow ratio, and the native perfusion index ( R2 = 0.699, df = 1, 60; F = 19.1, p Our experience in utilizing tcCO2 during CPB has demonstrated accuracy in estimating PaCO2 when compared to the gold standard arterial blood gas analysis, even during CO2 flooding of the surgical field.

In this article, we introduce a portable and low-cost ventilator that could be rapidly manufactured, to meet the increasing demand of ventilators worldwide produced by COVID-19 pandemic. These ventilators should be rapidly deployable and with functional capabilities to manage COVID-19 patients with severe acute respiratory distress syndrome (ARDS). Our implementation offers robustness, safety and functionality absent in existing solutions to the ventilator shortage (i.e., telemonitoring, easy-to-disinfect, modularity) by maintaining simplicity. The design makes use of a manual resuscitator as the core respiration component activated by a compression mechanism which consist of two electronically controlled paddles. The quality measurements obtained after testing on a calibrated artificial lung demonstrate repeatability and accuracy exceeding human capabilities of manual ventilation. The complete design files are provided in the supplementary materials to facilitate ventilator production even in resource-limited settings. The implementation of this mechanical ventilator could eliminate device rationing or splitting to serve multiple patients on ICUs. (C) 2021 Pontificia Universidad Catolica del Peru. Published by Elsevier Ltd. This work has been funded by the 055-2020-FONDECYT GRANT from the Peruvian government and the donations of the enterprises mentioned in our webpage: https://www.proyectomasi.pe/.In addition,the authors would like to thank to all the members of the Masi team, especially to all of the collaborators working at the five institutions involved in this project (BREIN, DIACSA, EAT, PUCP and Zolid). Without all of their effort, professionalism and sacrifice while working steadily during the pandemic; this device would have not existed.

The article considers the state of physiological indicators and morphological changes of internal organs during the application of long-term non-inhalation narcosis in pigs of two groups while providing artificial lung ventilation.

Background The COVID-19 pandemic has demonstrated the possibility of severe ventilator shortages in the near future. Objective We aimed to develop an acute shortage ventilator. Methods The ventilator was designed to mechanically compress a self-inflating bag resuscitator, using a modified ventilator patient circuit, which is controlled by a microcontroller and an optional laptop. It was designed to operate in both volume-controlled mode and pressure-controlled assist modes. We tested the ventilator in 4 modes using an artificial lung while measuring the volume, flow, and pressure delivered over time by the ventilator. Results The ventilator was successful in reaching the desired tidal volume and respiratory rates specified in national emergency use resuscitator system guidelines. The ventilator responded to simulated spontaneous breathing. Conclusions The key design goals were achieved. We developed a simple device with high performance for short-term use, made primarily from common hospital parts and generally available nonmedical components to avoid any compatibility or safety issues with the patient, and at low cost, with a unit cost per ventilator is less than $400 US excluding the patient circuit parts, that can be easily manufactured.

Graphical abstract, This study describes the development of a simple and easy-to-build portable automated bag valve mask (BVM) compression system, which, during acute shortages and supply chain disruptions can serve as a temporary emergency ventilator. The resuscitation system is based on the Arduino controller with a real-time operating system installed on a largely RepRap 3-D printable parametric component-based structure. The cost of the materials for the system is under $170, which makes it affordable for replication by makers around the world. The device provides a controlled breathing mode with tidal volumes from 100 to 800 mL, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4. The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach. Experimental results after testing on an artificial lung for peak inspiratory pressure (PIP), respiratory rate (RR), positive end-expiratory pressure (PEEP), tidal volume, proximal pressure, and lung pressure demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation. Future work is necessary to further develop and test the system to make it acceptable for deployment outside of emergencies such as with COVID-19 pandemic in clinical environments, however, the nature of the design is such that desired features are relatively easy to add using protocols and parametric design files provided.

Cardiovascular engineering and technology : CVET 13(2), 318-330 (2022). doi:10.1007/s13239-021-00579-y, Published by Springer, New York, NY

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.