Controlled generation of cell-laden hydrogel microspheres with core-shell scaffold mimicking microenvironment of tumor

Yuenan Li, Miaomiao Hai, Yu Zhao, Yalei Lv, Yi He, Guo Chen, Liyu Liu, Ruchuan Liu, Guigen Zhang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Development of an in vitro three-dimensional (3D) model that closely mimics actual environment of tissue has become extraordinarily important for anti-cancer study. In recent years, various 3D cell culture systems have been developed, with multicellular tumor spheroids being the most popular and effective model. In this work, we present a microfluidic device used as a robust platform for generating coreshell hydrogel microspheres with precisely controlled sizes and varied components of hydrogel matrix. To gain a better understanding of the governing mechanism of microsphere formation, computational models based on multiphase flow were developed to numerically model the droplet generation and velocity field evolution process with COMSOL Multiphysics software. Our modeling results show good agreement with experiments in size dependence on flow rate as well as effect of vortex flow on microsphere formation. With real-time tuning of the flow rates of aqueous phase and oil phase, tumor cells were encapsulated into the microspheres with controllable coreshell structure and different volume ratios of core (comprised of alginate, Matrigel, and/or Collagen) and shell (comprised of alginate). Viability of cells in four different hydrogel matrices were evaluated by standard acridine orange (AO) and propidium iodide (PI) staining. The proposed microfluidic system can play an important role in engineering the in vitro micro-environment of tumor spheroids to better mimic the actual in vivo 3D spatial structure of a tumor and perfect the 3D tumor models for more effective clinical therapies.

Original languageEnglish
Article number128703
JournalChinese Physics B
Issue number12
StatePublished - Dec 2018

Bibliographical note

Funding Information:
∗Project supported by the National Natural Science Foundation of China (Grant Nos. 11474345, 11674043, and 11604030) and the Fundamental and Advanced Research Program of Chongqing (Grant No. cstc2018jcyjAX0338). †These authors contributed equally to this work. ‡Corresponding author. E-mail: §Corresponding author. E-mail:

Publisher Copyright:
© 2018 Chinese Physical Society and IOP Publishing Ltd.


  • core-shell scaffold
  • microfluidics
  • phase field method
  • tumor spheroids

ASJC Scopus subject areas

  • Physics and Astronomy (all)


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