Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment
- Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment
- Hon Fai Chan; Ying Zhang; Yi-Ping Ho; Ya-Ling Chiu; 정영미; Kam W. Leong
- Issue Date
- Scientific Reports
- VOL 3, 3462-1-3462-8
- An attractive option for tissue engineering is to use of multicellular spheroids as microtissues, particularly
with stem cell spheroids. Conventional approaches of fabricating spheroids suffer from low throughput and
polydispersity in size, and fail to supplement cues from extracellular matrix (ECM) for enhanced
differentiation. In this study, we report the application of microfluidics-generated water-in-oil-in-water (w/
o/w) double-emulsion (DE) droplets as pico-liter sized bioreactor for rapid cell assembly and well-controlled
microenvironment for spheroid culture. Cells aggregated to form size-controllable (30–80 ㎛) spheroids in
DE droplets within 150 min and could be retrieved via a droplet-releasing agent. Moreover, precursor
hydrogel solution can be adopted as the inner phase to produce spheroid-encapsulated microgels after
spheroid formation. As an example, the encapsulation of human mesenchymal stem cells (hMSC) spheroids
in alginate and alginate-arginine-glycine-aspartic acid (-RGD) microgel was demonstrated, with enhanced
osteogenic differentiation further exhibited in the latter case.
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