title: A New Approach for On-Demand Generation of Various Oxygen Tensions for In Vitro Hypoxia Models.
abstract: The development of in vitro disease models closely mimicking the functions of human disease has captured increasing attention in recent years. Oxygen tensions and gradients play essential roles in modulating biological systems in both physiologic and pathologic events. Thus, controlling oxygen tension is critical for mimicking physiologically relevant in vivo environments for cell, tissue and organ research. We present a new approach for on-demand generation of various oxygen tensions for in vitro hypoxia models. Proof-of-concept prototypes have been developed for conventional cell culture microplate by immobilizing a novel oxygen-consuming biomaterial on the 3D-printed insert. For the first time, rapid (~3.8 minutes to reach 0.5% O2 from 20.9% O2) and precisely controlled oxygen tensions/gradients (2.68 mmHg per 50 μm distance) were generated by exposing the biocompatible biomaterial to the different depth of cell culture media. In addition, changing the position of 3D-printed inserts with immobilized biomaterials relative to the cultured cells resulted in controllable and rapid changes in oxygen tensions (<130 seconds). Compared to the current technologies, our approach allows enhanced spatiotemporal resolution and accuracy of the oxygen tensions. Additionally, it does not interfere with the testing environment while maintaining ease of use. The elegance of oxygen tension manipulation introduced by our new approach will drastically improve control and lower the technological barrier of entry for hypoxia studies. Since the biomaterials can be immobilized in any devices, including microfluidic devices and 3D-printed tissues or organs, it will serve as the basis for a new generation of experimental models previously impossible or very difficult to implement.
authors.affiliation: Cushing Neuromonitoring Laboratory, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Department of Neurosurgery, Hofstra Northwell School of Medicine, Manhasset, New York, United States of America.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Wayne
authors.initials: W
authors.lastname: Chaung
authors.affiliation: Department of Neurosurgery, Hofstra Northwell School of Medicine, Manhasset, New York, United States of America.
authors.forename: Cameron
authors.initials: C
authors.lastname: Mozayan
authors.affiliation: Cushing Neuromonitoring Laboratory, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Ranjeev
authors.initials: R
authors.lastname: Chabra
authors.affiliation: Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Cushing Neuromonitoring Laboratory, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Department of Neurosurgery, Hofstra Northwell School of Medicine, Manhasset, New York, United States of America.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Narayan
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002478:Cells, Cultured; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D056656:Lab-On-A-Chip Devices; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism*; D066330:Printing, Three-Dimensional; D051381:Rats
chemical_list: D001672:Biocompatible Materials; D010100:Oxygen