title: Gas Transfer in Cellularized Collagen-Membrane Gas Exchange Devices.
abstract: Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for 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, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have 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 remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m(2) of oxygen and ∼685 mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. 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 are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, 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.
authors.affiliation: 1 Department of Surgery, Center for Regenerative Medicine , Massachusetts General Hospital, Boston, Massachusetts.|2 Harvard Medical School , Boston, Massachusetts.|3 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts.
authors.forename: Justin H
authors.initials: JH
authors.lastname: Lo
authors.affiliation: 1 Department of Surgery, Center for Regenerative Medicine , Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Erik K
authors.initials: EK
authors.lastname: Bassett
authors.affiliation: 1 Department of Surgery, Center for Regenerative Medicine , Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Elliot J N
authors.initials: EJ
authors.lastname: Penson
authors.affiliation: 1 Department of Surgery, Center for Regenerative Medicine , Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: David M
authors.initials: DM
authors.lastname: Hoganson
authors.affiliation: 1 Department of Surgery, Center for Regenerative Medicine , Massachusetts General Hospital, Boston, Massachusetts.|2 Harvard Medical School , Boston, Massachusetts.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacanti
mesh_terms: D002448:Cell Adhesion; D003094:Collagen / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008567:Membranes, Artificial; D010100:Oxygen / Q000378:metabolism*
chemical_list: D008567:Membranes, Artificial; D003094:Collagen; D010100:Oxygen