Journal Article

A New Approach for On-Demand Generation of Various Oxygen Tensions for In Vitro Hypoxia Models

Wayne W. Chaung, Cameron Mozayan, Ping Wang, Ranjeev Chabra, Chunyan Li, Raj K. Narayan

2016

Overview

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.

• Publisher: Public Library of Science (PLoS),Public Library of Science
• Subject: 3-D printers / Animals / Anoxia / Apoptosis / Biocompatibility / Biocompatible Materials / Biocompatible Materials - chemistry / Biology and Life Sciences / Biomaterials / Biomedical materials / Cell culture / Cell Culture Techniques / Cell Culture Techniques - instrumentation / Cells, Cultured / Culture media / Disease / Enzymes / Glucose / Hydrogen peroxide / Hypoxia / Hypoxia - metabolism / In Vitro Techniques / In vivo methods and tests / Inserts / Ischemia / Lab-On-A-Chip Devices / Laboratories / Macrophages / Macrophages - cytology / Macrophages - metabolism / Media (culture) / Medical research / Medicine / Medicine and Health Sciences / Microfluidics / Mimicry / Models, Biological / Neurosurgery / Organs / Oxygen / Oxygen - metabolism / Oxygen tension / Physical Sciences / Physiological aspects / Printing, Three-Dimensional / Prototypes / Q / R / Rats / Research and Analysis Methods / Research Article / Rodents / Science / Stability / Stem cells / Tension / Three dimensional printing / Tumor necrosis factor-TNF