One Step Fabrication of Hydrogel Microcapsules with Hollow Core for Assembly and Cultivation of Hepatocyte Spheroids

Publication date: Available online 6 January 2017
Source:Acta Biomaterialia
Author(s): Christian Siltanen, Michaela Diakataou, Jeremy Lowen, Amranul Haque, Ali Rahimian, Gulnaz Stybayeva, Alexander Revzin
3D hepatic microtissues can serve as valuable liver analogues for cell-based therapies and for hepatotoxicity screening during preclinical drug development. However, hepatocytes rapidly dedifferentiate in vitro, and typically require 3D cultures systems or co-cultures for phenotype rescue. In this work we present a novel microencapsulation strategy, utilizing coaxial flow-focusing droplet microfluidics to fabricate microcapsules with liquid core and poly(ethylene glycol) (PEG) shell. When entrapped inside these capsules, primary hepatocytes rapidly formed cell-cell contacts and assembled into compact spheroids. High levels of hepatic function were maintained inside the capsules for over ten days. The microencapsulation approach described here is compatible with difficult-to-culture primary epithelial cells, allows for tuning gel mechanical properties and diffusivity, and may be used in the future for high density suspension cell cultures.Statement of significanceOur paper combines an interesting new way for making capsules with cultivation of difficult-to-maintain primary epithelial cells (hepatocytes). The microcapsules described here will enable high density suspension culture of hepatocytes or other cells and may be used as building blocks for tissue engineering applications.

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