Cell-laden microgel prepared using a biocompatible aqueous two-phase strategy
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Microfluidic methods are frequently used to produce cell-laden microgels for various biomedical purposes. Such microfluidic methods generally employ oil-water systems. The poor distribution of crosslinking reagents in the oil phase limits the available gelation strategies. Extracting the microgel from the oil-phase also reduces its production efficiency. In this study, an aqueous two-phase system (ATPS) involving dextran (DEX) and polyethylene glycol (PEG) was used to prepare cell-laden microgel. This avoided the problems associated with an oil phase. The microgel precursor polymers and crosslinking reagents were dispersed in the DEX and PEG phases, respectively. The ultra-low interfacial tension of the ATPS hindered droplet formation. A co-flow microfluidic device was fabricated to overcome this problem. The device incorporated a square-wave-changing injection force, to improve the efficiency of droplet formation. The microgel precursor (including alginate and carboxymethyl cellulose derivatives possessing phenolic hydroxyl moieties) could be dispersed in the DEX solution at various concentrations. Uniform droplets were formed with controllable diameters, and were sequentially converted to microgel by horseradish peroxidase-catalyzed crosslinking. Cells were dispersed in the DEX phase with the microgel precursor polymer, and retained their high viability and proliferation in the resulting microgel. The solubility of gelatin derivatives in the DEX phase was low, but was sufficient to impart cell adhesion properties on the microgel.
KeywordsAqueous two-phase system Microfluidics Microgel Cell adhesion Cell encapsulation
We thank Dr. Yoshihiro Ojima, Osaka City University, Osaka, Japan, for providing an Elveflow OB1 microfluidic flow controller and for constructing the microfluids. This research was supported by the Young Researchers Career Support Program (Grant no. j881100933) of Osaka University, the Multi-disciplinary Research Laboratory System (Grant no. 1119902199) of the Graduate School of Engineering Science, Osaka University, and the Nanotechnology Platform Project (Nanotechnology Open Facilities in Osaka University) (Grant no. F-16-OS-0012) of the Ministry of Education, Culture, Sports, Science and Technology, Japan.
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Conflict of interest
The authors have no conflict of interest directly relevant to the content of this article.
Preparation of microgel using the DEX/PEG-based aqueous system. The DEX-based solution and PEG solution with H2O2 were stained with red and blue food colorings, respectively. (MP4 3456 kb)
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