A liver-on-a-chip platform with bioprinted hepatic spheroids

Nupura S. Bhise, Vijayan Manoharan, Solange Massa, Ali Tamayol, Masoumeh Ghaderi, Mario Miscuglio, Qi Lang, Yu Shrike Zhang, Su Ryon Shin, Giovanni Calzone, Nasim Annabi, Thomas D. Shupe, Colin E. Bishop, Anthony Atala, Mehmet R. Dokmeci, Ali Khademhosseini

Research output: Contribution to journalArticle

196 Scopus citations

Abstract

The inadequacy of animal models in correctly predicting drug and biothreat agent toxicity in humans has resulted in a pressing need for in vitro models that can recreate the in vivo scenario. One of the most important organs in the assessment of drug toxicity is liver. Here, we report the development of a liver-on-a-chip platform for long-term culture of three-dimensional (3D) human HepG2/C3A spheroids for drug toxicity assessment. The bioreactor design allowed for in situ monitoring of the culture environment by enabling direct access to the hepatic construct during the experiment without compromising the platform operation. The engineered bioreactor could be interfaced with a bioprinter to fabricate 3D hepatic constructs of spheroids encapsulated within photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. The engineered hepatic construct remained functional during the 30 days culture period as assessed by monitoring the secretion rates of albumin, alpha-1 antitrypsin, transferrin, and ceruloplasmin, as well as immunostaining for the hepatocyte markers, cytokeratin 18, MRP2 bile canalicular protein and tight junction protein ZO-1. Treatment with 15 mM acetaminophen induced a toxic response in the hepatic construct that was similar to published studies on animal and other in vitro models, thus providing a proof-of-concept demonstration of the utility of this liver-on-a-chip platform for toxicity assessment.

Original languageEnglish (US)
Article number014101
JournalBiofabrication
Volume8
Issue number1
DOIs
StatePublished - Jan 12 2016

Keywords

  • 3D culture
  • bioprinting
  • bioreactor
  • drug toxicity
  • hepatocytes
  • liver

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'A liver-on-a-chip platform with bioprinted hepatic spheroids'. Together they form a unique fingerprint.

  • Cite this

    Bhise, N. S., Manoharan, V., Massa, S., Tamayol, A., Ghaderi, M., Miscuglio, M., Lang, Q., Zhang, Y. S., Shin, S. R., Calzone, G., Annabi, N., Shupe, T. D., Bishop, C. E., Atala, A., Dokmeci, M. R., & Khademhosseini, A. (2016). A liver-on-a-chip platform with bioprinted hepatic spheroids. Biofabrication, 8(1), [014101]. https://doi.org/10.1088/1758-5090/8/1/014101