One step fabrication of hydrogel microcapsules with hollow core for assembly and cultivation of hepatocyte spheroids

Christian Siltanen, Michaela Diakataou, Jeremy Lowen, Amranul Haque, Ali Rahimian, Gulnaz Stybayeva, Alexander Revzin

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 culture 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) gel 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 Significance Our 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 engineering tissues.

Original languageEnglish (US)
Pages (from-to)428-436
Number of pages9
JournalActa Biomaterialia
Volume50
DOIs
StatePublished - Mar 1 2017

Fingerprint

Hydrogel
Hydrogels
Capsules
Hepatocytes
Microencapsulation
Fabrication
Drug Compounding
Polyethylene glycols
Gels
Liver
Suspensions
Epithelial Cells
Tissue engineering
Cell culture
Microfluidics
Ethylene Glycol
Tissue Engineering
Cell- and Tissue-Based Therapy
Screening
Coculture Techniques

Keywords

  • Droplet generation
  • Hepatocytes
  • Hydrogel microcapsules
  • Microfluidic fabrication

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

One step fabrication of hydrogel microcapsules with hollow core for assembly and cultivation of hepatocyte spheroids. / Siltanen, Christian; Diakataou, Michaela; Lowen, Jeremy; Haque, Amranul; Rahimian, Ali; Stybayeva, Gulnaz; Revzin, Alexander.

In: Acta Biomaterialia, Vol. 50, 01.03.2017, p. 428-436.

Research output: Contribution to journalArticle

Siltanen, Christian ; Diakataou, Michaela ; Lowen, Jeremy ; Haque, Amranul ; Rahimian, Ali ; Stybayeva, Gulnaz ; Revzin, Alexander. / One step fabrication of hydrogel microcapsules with hollow core for assembly and cultivation of hepatocyte spheroids. In: Acta Biomaterialia. 2017 ; Vol. 50. pp. 428-436.
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