Cellularized Collagen-Membrane Lung Assist Devices for Efficient Gas Transfer
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CitationLo, Justin H. 2017. Cellularized Collagen-Membrane Lung Assist Devices for Efficient Gas Transfer. Doctoral dissertation, Harvard Medical School.
AbstractChronic lower respiratory disease afflicts over 5% of the United States population, leading to over 145,000 deaths annually. There remains a need for safer and more durable alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, though harnessing their potential depends on efficient and biocompatible design. Incorporating biomimetic materials into such devices can help replicate efficient native gas exchange function and additionally support cellular components. In this work, we developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in membrane remodeling, reflected by reductions in membrane thickness. Functionally, these collagen-membrane lung devices in the acellular configuration mediated effective gas exchange up to rates of ~288 mL/min/m^2 O2 transfer and ~685 mL/min/m^2 CO2 transfer, approaching the gas exchange efficiency measured in the native lung. After testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects were relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate – limited primarily by shear forces experienced by blood components. Finally, collagen-membrane devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32676121