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

Abstract

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.

A microfluidic lung‐on‐a‐chip based on biomimetic hydrogel membrane

“…A better understanding of the assumed beneficial role of soft hydrogel membrane over the stiff PDMS counterparts in such membrane‐based models on the establishment of more functional and physiological lungs in vitro could change the design and performance of such lung‐on‐a‐chip. Although the hydrogel membrane still has limitations on their high thickness and requirement on surface modification, the robustness property and large availability afford them great potential application in construction of artificial lung in future (Astor & Borenstein, 2022; Kovach et al, 2015).…”

“…Although the hydrogel membrane still has limitations on their high thickness and requirement on surface modification, the robustness property and large availability afford them great potential application in construction of artificial lung in future (Astor & Borenstein, 2022;Kovach et al, 2015).…”

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

“…The microfluidic design reported here is motivated by the opportunity to address limitations of traditional HFMO in terms of blood health, by recapitulating key aspects of the microcirculation such as vessel dimensions designed for optimum oxygen transfer and minimal pressure drop as well as flow patterns that allow for smooth transitions between large high‐flow distribution channels and the small, low‐flow channels where oxygen transfer primarily occurs. [ 56 ] While considerable progress has already been made in advancing microfluidic ECMO toward clinical relevance, three areas have been particularly lacking in the field: tight control of shear stress at all points in the network, scalable operation at clinically relevant flow rates, and stable long‐term performance. We believe that the data presented here represent a major step forward on all three fronts and demonstrate a clear path to further improved performance.…”

Toward 3D printed microfluidic artificial lungs for respiratory support

“…5 These risks stem from hemocompatibility challenges with the hollow-fiber oxygenators used in the clinic. 3,4 During oxygenation, the blood traverses a dense bundle of gas-permeable hollow fibers, experiencing non-physiological flow paths and shear stresses, triggering the blood coagulation cascade and inflammatory responses in the patient. 4,6,7 Further, this design has suboptimal gas exchange relative to the native lungs.…”

“…3,4 During oxygenation, the blood traverses a dense bundle of gas-permeable hollow fibers, experiencing non-physiological flow paths and shear stresses, triggering the blood coagulation cascade and inflammatory responses in the patient. 4,6,7 Further, this design has suboptimal gas exchange relative to the native lungs. In the alveolar microenvironment where oxygenation occurs, capillaries are about 10 μm across and their cell walls are around 1-3 μm thick.…”