Hollow Fiber Membrane Oxygenator Research Articles

An endothelium membrane mimetic antithrombotic coating enables safer and longer extracorporeal membrane oxygenation application

Thrombosis and plasma leakage are two of the most frequent dysfunctions of polypropylene (PP) hollow fiber membrane (PPM) used in extracorporeal membrane oxygenation (ECMO) therapy. In this study, a superhydrophilic endothelial membrane mimetic coating (SEMMC) was constructed on polydopamine-polyethyleneimine pre-coated surfaces of the PPM oxygenator and its ECMO circuit to explore safer and more sustainable ECMO strategy. The SEMMC is fabricated by multi-point anchoring of a phosphorylcholine and carboxyl side chained copolymer (PMPCC) and grafting of heparin (Hep) to form PMPCC-Hep interface, which endows the membrane superior hemocompatibility and anticoagulation performances. Furthermore, the modified PPM reduces protein adsorption amount to less than 30 ng/cm2. More significantly, the PMPCC-Hep coated ECMO system extends the anti-leakage and non-clotting oxygenation period to more than 15 h in anticoagulant-free animal extracorporeal circulation, much better than the bare and conventional Hep coated ECMO systems with severe clots and plasma leakage in 4 h and 8 h, respectively. This SEMMC strategy of grafting bioactive heparin onto bioinert zwitterionic copolymer interface has great potential in developing safer and longer anticoagulant-free ECMO systems. Statement of significanceA superhydrophilic endothelial membrane mimetic coating was constructed on surfaces of polypropylene hollow fiber membrane (PPM) oxygenator and its ECMO circuit by multi-point anchoring of a phosphorylcholine and carboxyl side chain copolymer (PMPCC) and grafting of heparin (Hep). The strong antifouling nature of the PMPCC-Hep coating resists the adsorption of plasma bio-molecules, resulting in enhanced hemocompatibility and anti-leakage ability. The grafted heparin on the zwitterionic PMPCC interface exhibits superior anticoagulation property. More significantly, the PMPCC-Hep coating achieves an extracorporeal circulation in a pig model for at least 15 h without any systemic anticoagulant. This endothelial membrane mimetic anticoagulation strategy shows great potential for the development of safer and longer anticoagulant-free ECMO systems.

First 24-Hour-Long Intensive Care Unit Testing of a Clinical-Scale Microfluidic Oxygenator in Swine: A Safety and Feasibility Study.

Microfluidic membrane oxygenators are designed to mimic branching vasculature of the native lung during extracorporeal lung support. To date, scaling of such devices to achieve clinically relevant blood flow and lung support has been a limitation. We evaluated a novel multilayer microfluidic blood oxygenator (BLOx) capable of supporting 750-800 ml/min blood flow versus a standard hollow fiber membrane oxygenator (HFMO) in vivo during veno-venous extracorporeal life support for 24 hours in anesthetized, mechanically ventilated uninjured swine (n = 3/group). The objective was to assess feasibility, safety, and biocompatibility. Circuits remained patent and operated with stable pressures throughout 24 hours. No group differences in vital signs or evidence of end-organ damage occurred. No change in plasma free hemoglobin and von Willebrand factor multimer size distribution were observed. Platelet count decreased in BLOx at 6 hours (37% dec, P = 0.03), but not in HFMO; however, thrombin generation potential was elevated in HFMO (596 ± 81 nM·min) versus BLOx (323 ± 39 nM·min) at 24 hours ( P = 0.04). Other coagulation and inflammatory mediator results were unremarkable. BLOx required higher mechanical ventilator settings and showed lower gas transfer efficiency versus HFMO, but the stable device performance indicates that this technology is ready for further performance scaling and testing in lung injury models and during longer use conditions.

PULM5: Hyperbaric Blood Oxygenation – Basic Considerations and First Results

Hyperbaric oxygen therapy is beneficial in several applications, but hyperbaric chambers are scarce. We are developing a novel technology for extracorporeal hyperbaric blood oxygenation (HBOX). This extracorporeal procedure uses pressure to increase the oxygen (O2) concentration in blood. The technology can provide support when large amounts of oxygen are needed: In the treatment of CO poisoning the dissolved oxygen displaces the CO from the blood, removing it from the organism. This way, the oxygen deficiency can be ended rapidly, reducing or preventing secondary damage that frequently occurs. In acute respiratory failure (ARF) the HBOX technology can support lung function, by significantly increasing oxygen transport across a specific membrane area, while maintaining adequate CO2-removal. The prototype of the HBOX consists of 2 roller pumps with a hollow-fiber membrane oxygenator (HFMO) placed in between, a control unit for gas and blood flow and a double lumen catheter. By varying the flow rates of the roller pumps, excess pressure is generated in the HFMO without causing significant blood damage. Simultaneously, the oxygen pressure in the HFMO is increased, allowing for hyperbaric oxygenation. To avoid bubble formation, either O2 increase is limited, or excess O2 is removed in second HFMO before reinfusion. The prototype was tested in-vitro using porcine blood that was either CO poisoned or conditioned to mimic ARF. In acute in-vivo experiments for CO poisoning, we used CO-poisoned pigs (ca. 75 kg, COHb = 43 %, n = 3). For in-vivo experiments for ARF, 70 kg sheep were used with ventilator settings simulating respiratory failure, resulting in SaO2 = 69 %, paCO2 = 72 mmHg (n = 2). In-vitro test results show that the HBOX can fully oxygenate hypoxic blood (sO2 ca. 40 %) with a hilite 800 LT at a flow rate of 2 L/min, which is twice the amount of oxygen transferred, compared to conventional mode, Fig. 1. In in-vivo trials, the CO elimination rate from the animals’ blood doubled when using HBOX + oxygen mask compared to oxygen mask alone, see Fig. 2. In the ARF trials, the HBOX approach resulted in SaO2 of 89, 95, and 99 % and paCO2 was 49, 46, and 39 mmHg at blood flows of 0.5, 1.0, and 1.5 L/min, respectively, see Fig. 3. The HBOX is a promising approach to increase oxygen transport across a specific membrane area. The increased oxygen levels can be used for efficient extracorporeal CO removal. For respiratory support, the hyperbaric technology adds a new dimension to ECMO treatment, allowing the use of smaller oxygenators, potentially reducing the need for anticoagulation, as well as inflammatory responses and thus invasiveness. The hyperbaric technology can be used gradually, so that the membrane efficiency can be increased during intervention. This allows us to build an oxygenator with an ideal flow distribution over a wide range of blood flows, which avoids thrombus formation in the device at lower blood flows.Figure 1. Laboratory results oxygenation performanceFigure 2. Elimination rate COHb in in-vivo trialsFigure 3. Arterial blood gases during in-vivo trial for ARF

A Clinical-Scale Microfluidic Respiratory Assist Device with 3D Branching Vascular Networks.

Recent global events such as COVID-19 pandemic amid rising rates of chronic lung diseases highlight the need for safer, simpler, and more available treatments for respiratory failure, with increasing interest in extracorporeal membrane oxygenation (ECMO). A key factor limiting use of this technology is the complexity of the blood circuit, resulting in clotting and bleeding and necessitating treatment in specialized care centers. Microfluidic oxygenators represent a promising potential solution, but have not reached the scale or performance required for comparison with conventional hollow fiber membrane oxygenators (HFMOs). Here the development and demonstration of the first microfluidic respiratory assist device at a clinical scale is reported, demonstrating efficient oxygen transfer at blood flow rates of 750mLmin⁻1 , the highest ever reported for a microfluidic device. The central innovation of this technology is a fully 3D branching network of blood channels mimicking key features of the physiological microcirculation by avoiding anomalous blood flows that lead to thrombus formation and blood damage in conventional oxygenators. Low, stable blood pressure drop, low hemolysis, and consistent oxygen transfer, in 24-hour pilot large animal experiments are demonstrated - a key step toward translation of this technology to the clinic for treatment of a range of lung diseases.

Evolutions of extracorporeal membrane oxygenator (ECMO): perspectives for advanced hollow fiber membrane.

Hollow fiber membrane is incorporated into an extracorporeal membrane oxygenator (ECMO), and the function of the membrane determines the ECMO's functions, such as gas transfer rate, biocompatibility, and durability. In Japan, the membrane oxygenator to assist circulation and ventilation is approved for ECMO support. However, in all cases, the maximum use period has been only 6h, and so-called 'off-label use' is common for ECMO support of severely ill COVID-19 patients. Under these circumstances, the HLS SET Advanced (Getinge Group Japan K.K.) was approved in 2020 for the first time in Japan as a membrane oxygenator with a two-week period of use. Following this membrane oxygenator, it is necessary to establish a domestic ECMO system that is approved for long-term use and suitable for supporting patients. Looking back on the evolution of ECMO so far, Japanese researchers and manufacturers have also contributed to the developments of ECMO globally. Currently, excellent membrane oxygenators and systems have been marketed by Japanese manufacturers and some of them are globally acclaimed, but in fact, most of the ECMO membranes are not made in Japan. Fortunately, Japan has led the world in the fields of membrane separation technology and hollow fiber membrane production. In the wake of this pandemic, from the perspective of medical and economic security, the practical use of purely domestic hollow fiber membranes and membrane oxygenators for long-term ECMO is imperative in anticipation of the next pandemic.

Improvement of a Mathematical Model to Predict CO2 Removal in Hollow Fiber Membrane Oxygenators.

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.

A fibrin enhanced thrombosis model for medical devices operating at low shear regimes or large surface areas.

Over the past decade, much of the development of computational models of device-related thrombosis has focused on platelet activity. While those models have been successful in predicting thrombus formation in medical devices operating at high shear rates (> 5000 s-1), they cannot be directly applied to low-shear devices, such as blood oxygenators and catheters, where emerging information suggest that fibrin formation is the predominant mechanism of clotting and platelet activity plays a secondary role. In the current work, we augment an existing platelet-based model of thrombosis with a partial model of the coagulation cascade that includes contact activation of factor XII and fibrin production. To calibrate the model, we simulate a backward-facing-step flow channel that has been extensively characterized in-vitro. Next, we perform blood perfusion experiments through a microfluidic chamber mimicking a hollow fiber membrane oxygenator and validate the model against these observations. The simulation results closely match the time evolution of the thrombus height and length in the backward-facing-step experiment. Application of the model to the microfluidic hollow fiber bundle chamber capture both gross features such as the increasing clotting trend towards the outlet of the chamber, as well as finer local features such as the structure of fibrin around individual hollow fibers. Our results are in line with recent findings that suggest fibrin production, through contact activation of factor XII, drives the thrombus formation in medical devices operating at low shear rates with large surface area to volume ratios.

The microfluidic artificial lung: Mimicking nature's blood path design to solve the biocompatibility paradox.

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.

Extracorporeal Hyperoxygenation Therapy (EHT) for Carbon Monoxide Poisoning: In-Vitro Proof of Principle.

Carbon monoxide (CO) poisoning is the leading cause of poisoning-related deaths globally. The currently available therapy options are normobaric oxygen (NBO) and hyperbaric oxygen (HBO). While NBO lacks in efficacy, HBO is not available in all areas and countries. We present a novel method, extracorporeal hyperoxygenation therapy (EHT), for the treatment of CO poisoning that eliminates the CO by treating blood extracorporeally at elevated oxygen partial pressure. In this study, we proof the principle of the method in vitro using procine blood: Firstly, we investigated the difference in the CO elimination of a hollow fibre membrane oxygenator and a specifically designed batch oxygenator based on the bubble oxygenator principle at elevated pressures (1, 3 bar). Secondly, the batch oxygenator was redesigned and tested for a broader range of pressures (1, 3, 5, 7 bar) and temperatures (23, 30, 37 °C). So far, the shortest measured carboxyhemoglobin half-life in the blood was 21.32 min. In conclusion, EHT has the potential to provide an easily available and effective method for the treatment of CO poisoning.

A high gas transfer efficiency microfluidic oxygenator for extracorporeal respiratory assist applications in critical care medicine.

Advances in microfluidics technologies have spurred the development of a new generation of microfluidic respiratory assist devices, constructed using microfabrication techniques capable of producing microchannel dimensions similar to those found in human capillaries and gas transfer films in the same thickness range as the alveolar membrane. These devices have been tested in laboratory settings and in some cases in extracorporeal animal experiments, yet none have been advanced to human clinical studies. A major challenge in the development of microfluidic oxygenators is the difficulty in scaling the technology toward high blood flows necessary to support adult humans; such scaling efforts are often limited by the complexity of the fabrication process and the manner in which blood is distributed in a three-dimensional network of microchannels. Conceptually, a central advantage of microfluidic oxygenators over existing hollow-fiber membrane-based configurations is the potential for shallower channels and thinner gas transfer membranes, features that reduce oxygen diffusion distances, to result in a higher gas transfer efficiency defined as the ratio of the volume of oxygen transferred to the blood per unit time to the active surface area of the gas transfer membrane. If this ratio is not significantly higher than values reported for hollow fiber membrane oxygenators (HFMO), then the expected advantage of the microfluidic approach would not be realized in practice, potentially due to challenges encountered in blood distribution strategies when scaling microfluidic designs to higher flow rates. Here, we report on scaling of a microfluidic oxygenator design from 4 to 92mL/min blood flow, within an order of magnitude of the flow rate required for neonatal applications. This scaled device is shown to have a gas transfer efficiency higher than any other reported system in the literature, including other microfluidic prototypes and commercial HFMO cartridges. While the high oxygen transfer efficiency is a promising advance toward clinical scaling of a microfluidic architecture, it is accompanied by an excessive blood pressure drop in the circuit, arising from a combination of shallow gas transfer channels and equally shallow distribution manifolds. Therefore, next-generation microfluidic oxygenators will require novel design and fabrication strategies to minimize pressure drops while maintaining very high oxygen transfer efficiencies.

In silico simulation of the liquid phase pressure drop through cylindrical hollow‐fiber membrane oxygenators using a modified phenomenological model

AbstractLow blood pressure drop is an important performance characteristic of a hollow‐fiber membrane oxygenator (HFMO). While the application of natural blood corresponds to complex handling procedures, the in vitro investigation of liquid pressure drop is mainly done using water or similar fluids (e.g., normal saline solution [NSS]). In this study, a comprehensive phenomenological model has been proposed to predict the liquid pressure drop through a cylindrical HFMO, considering viscous and inertial resistances in porous media, derived from literature. The results demonstrate that approaches based on Darcy–Weisbach phenomenological equation correlate the most with in vitro experimental investigations using NSS and native porcine blood, in both pediatric and adult commercially available cylindrical HFMOs. Remarkably, this study corroborates theoretically and experimentally that approaches based on Ergun semi‐empirical equation fail to predict the liquid pressure drop in cylindrical HFMOs. Moreover, it is shown that the presented phenomenological model is also applicable to cylindrical hollow‐fiber heat exchangers, and subsequently, its noticeable effect on total liquid pressure drop through cylindrical HFMOs is demonstrated. The results reveal that this component may contribute to almost half of total blood pressure drop, and therefore, it should be redesigned using other approaches than hollow fibers.

Hemodynamic Assessment of Hollow-Fiber Membrane Oxygenators Using Computational Fluid Dynamics in Heterogeneous Membrane Models.

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.

International Pediatric Perfusion Practice: 2016 Survey Results

New cardiopulmonary bypass device techniques emerge and are reported in the scientific literature. The extent to which they are actually adopted into clinical practice is not well known. Since 1989, we have periodically surveyed pediatric cardiac centers to ascertain practice patterns. In December 2016, a 186-question perfusion survey was distributed to pediatric cardiac surgery centers all over the world using a Web-based survey tool. Responses were received from 93 North American (NA) centers (the United States and Canada) and 67 non–NA (NNA) centers, representing 19,645 cumulative annual procedures in NA and 27,776 in NNA centers on patients <18 years. Wide variation in practice was evident across geographic regions. However, the most common pediatric circuit consisted of a hard-shell (open) venous reservoir, an arterial roller pump, and a hollow-fiber membrane oxygenator with a separate or integrated arterial filter. Compared with our previous surveys, there was increased utilization of all types of safety devices. The use of an electronic perfusion record was reported by 50% of NA centers and 31% of NNA centers. There was wide regional variation in cardioplegia delivery systems and cardioplegia solutions. Seventy-nine percent of the centers reported the use of some form of modified ultrafiltration. The survey demonstrated that there remains variation in perfusion practice for pediatric patients. Future surveys will be useful to evaluate the adoption of emerging perfusion practice guidelines.

International Pediatric Perfusion Practice: 2016 Survey Results.

New cardiopulmonary bypass device techniques emerge and are reported in the scientific literature. The extent to which they are actually adopted into clinical practice is not well known. Since 1989, we have periodically surveyed pediatric cardiac centers to ascertain practice patterns. In December 2016, a 186-question perfusion survey was distributed to pediatric cardiac surgery centers all over the world using a Web-based survey tool. Responses were received from 93 North American (NA) centers (the United States and Canada) and 67 non-NA (NNA) centers, representing 19,645 cumulative annual procedures in NA and 27,776 in NNA centers on patients <18 years. Wide variation in practice was evident across geographic regions. However, the most common pediatric circuit consisted of a hard-shell (open) venous reservoir, an arterial roller pump, and a hollow-fiber membrane oxygenator with a separate or integrated arterial filter. Compared with our previous surveys, there was increased utilization of all types of safety devices. The use of an electronic perfusion record was reported by 50% of NA centers and 31% of NNA centers. There was wide regional variation in cardioplegia delivery systems and cardioplegia solutions. Seventy-nine percent of the centers reported the use of some form of modified ultrafiltration. The survey demonstrated that there remains variation in perfusion practice for pediatric patients. Future surveys will be useful to evaluate the adoption of emerging perfusion practice guidelines.

Computation of Global and Local Mass Transfer in Hollow Fiber Membrane Modules

Computational fluid dynamics (CFD) provides a flexible tool for investigation of separation processes within membrane hollow fiber modules. By enabling a three-dimensional and time dependent description of the corresponding transport phenomena, very detailed information about mass transfer or geometrical influences can be provided. The high level of detail comes with high computational costs, especially since species transport simulations must discretize and resolve steep gradients in the concentration polarization layer at the membrane. In contrast, flow simulations are not required to resolve these gradients. Hence, there is a large gap in the scale and complexity of computationally feasible geometries when comparing flow and species transport simulations. A method, which tries to cover the mentioned gap, is presented in the present article. It allows upscaling of the findings of species transport simulations, conducted for reduced geometries, on the geometrical scales of flow simulations. Consequently, total transmembrane transport of complete modules can be numerically predicted. The upscaling method does not require any empirical correlation to incorporate geometrical characteristics but solely depends on results acquired by CFD flow simulations. In the scope of this research, the proposed method is explained, conducted, and validated. This is done by the example of CO2 removal in a prototype hollow fiber membrane oxygenator.

Pumping O2 with no N2: An Overview of Hollow Fiber Membrane Oxygenators with Integrated Arterial Filters.

The advancement of cardiac surgery benefits from the continual technological progress of cardiopulmonary bypass (CPB). Every improvement in the CPB technology requires further clinical and laboratory tests to prove its safety and effectiveness before it can be widely used in clinical practice. In order to reduce the priming volume and eliminate a separate arterial filter in the CPB circuit, several manufacturers developed novel hollow-fiber membrane oxygenators with integrated arterial filters (IAF). Clinical and experimental studies demonstrated that an oxygenator with IAF could reduce total priming volume, blood donor exposure and gaseous microemboli delivery to the patient. It can be easily set up and managed, simplifying the CPB circuit without sacrificing safety. An oxygenator with IAF is expected to be more beneficial to the patients with low body weight and when using a minimized extracorporeal circulation system. The aim of this review manuscript was to discuss briefly the concept of integration, the current oxygenators with IAF, and the in-vitro / in-vivo performance of the oxygenators with IAF.

Fully Resolved Computational (CFD) and Experimental Analysis of Pressure Drop and Blood Gas Transport in a Hollow Fibre Membrane Oxygenator Module

Membrane oxygenators or artificial lungs have become a reliable and live saving clinical technique. To limit side effects on blood platelet parameters the high extrinsic surface introduced by the hollow fiber membrane packing has to be decreased. This adjustment must be accompanied with an improvement of gas exchange performance to guarantee sufficient blood gas transfer. Computational fluid dynamics (CFD) provides a spatial and temporal resolution of the membrane oxygenation process and enables systematic optimization of artificial lungs. In scope of this research a new CFD approach to examine the gas exchange performance of oxygenators was developed. Blood and sweep gas flow in the fiber packing as well as blood gas exchange through the membrane between blood and sweep fluid are fully resolved and simulated. The results were compared to in vitro experiments comprising determination of blood side pressure loss and CO2 exchange performance of a prototype membrane module. While flow simulations were conducted for the complete prototype module, gas exchange simulations were limited to a representative fiber packing segment. The presented simulation approach provides a basis for the design of future artificial lungs.

A pH‐based experimental method for carbon dioxide exchange evaluation in cylindrical hollow fiber membrane oxygenators

AbstractCarbon dioxide transfer rate (CTR) is an important performance characteristic of a hollow fiber membrane oxygenator (HFMO), which is used as an artificial lung in clinical practices. In vitro measurement of CTR through HFMOs is challenging specifically in investigations with natural blood. In this study, a straightforward and applicable method is presented in order to simulate blood CO2 exchange through HFMOs and consequently calculate the corresponding CTR. The method is based on CO2 dissociation in deionized water resulting in pH drop of the aqueous solution. The results of proposed method are then validated comparing with in vitro investigations using native porcine blood (NPB) in two types of commercially available HFMOs. Moreover, an innovative relationship between effective membrane surface area, blood retention time, and mixing ratio of CO2 and N2 gases in pH drop experiment is introduced in order to simulate the CTR of complicated NPB investigations. The results reveal a good agreement between pH‐based calculated CTRs and those investigated conventionally using NPB. This method would be principally applicable not only for other cylindrical HFMOs but also for other configurations of hollow fiber membrane contactors.

Zwitterionic poly-carboxybetaine coating reduces artificial lung thrombosis in sheep and rabbits

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. Statement of SignificanceChronic 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.

Defining the optimal duration for normothermic regional perfusion in the kidney donor: A porcine preclinical study.

Kidneys from donation after circulatory death (DCD) are highly sensitive to ischemia-reperfusion injury and thus require careful reconditioning, such as normothermic regional perfusion (NRP). However, the optimal NRP protocol remains to be characterized. NRP was modeled in a DCD porcine model (30minutes of cardiac arrest) for 2, 4, or 6hours compared to a control group (No-NRP); kidneys were machine-preserved and allotransplanted. NRP appeared to permit recovery from warm ischemia, possibly due to an increased expression of HIF1α-dependent survival pathway. At 2hours, blood levels of ischemic injury biomarkers increased: creatinine, lactate/pyruvate ratio, LDH, AST, NGAL, KIM-1, CD40 ligand, and soluble-tissue-factor. All these markers then decreased with time; however, AST, NGAL, and KIM-1 increased again at 6hours. Hemoglobin and platelets decreased at 6hours, after which the procedure became difficult to maintain. Regarding inflammation, active tissue-factor, cleaved PAR-2 and MCP-1 increased by 4-6hours, but not TNF-α and iNOS. Compared to No-NRP, NRP kidneys showed lower resistance during hypothermic machine perfusion (HMP), likely associated with pe-NRP eNOS activation. Kidneys transplanted after 4 and 6hours of NRP showed better function and outcome, compared to No-NRP. In conclusion, our results confirm the mechanistic benefits of NRP and highlight 4hours as its optimal duration, after which injury markers appear.