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Chin. Phys. B, 2018, Vol. 27(12): 128703    DOI: 10.1088/1674-1056/27/12/128703
INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY Prev   Next  

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

Yuenan Li(李岳南)1, Miaomiao Hai(海苗苗)1, Yu Zhao(赵宇)2, Yalei Lv(吕亚蕾)1, Yi He(何益)1, Guo Chen(陈果)1, Liyu Liu(刘雳宇)1, Ruchuan Liu(刘如川)1, Guigen Zhang2
1 Department of Physics, Chongqing University, Chongqing 401331, China;
2 Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506, USA
Abstract  

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 core-shell 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 core-shell 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.

Keywords:  microfluidics      core-shell scaffold      phase field method      tumor spheroids  
Received:  02 May 2018      Revised:  26 September 2018      Accepted manuscript online: 
PACS:  87.80.-y (Biophysical techniques (research methods))  
  87.64.Aa (Computer simulation)  
Fund: 

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).

Corresponding Authors:  Ruchuan Liu, Guigen Zhang     E-mail:  phyliurc@cqu.edu.cn;guigen.bme@uky.edu

Cite this article: 

Yuenan Li(李岳南), Miaomiao Hai(海苗苗), Yu Zhao(赵宇), Yalei Lv(吕亚蕾), Yi He(何益), Guo Chen(陈果), Liyu Liu(刘雳宇), Ruchuan Liu(刘如川), Guigen Zhang Controlled generation of cell-laden hydrogel microspheres with core-shell scaffold mimicking microenvironment of tumor 2018 Chin. Phys. B 27 128703

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