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

doi:10.1088/1674-1056/27/12/128703

中国物理B ›› 2018, Vol. 27 ›› Issue (12): 128703-128703.doi: 10.1088/1674-1056/27/12/128703

• INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY • 上一篇下一篇

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

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

1 Department of Physics, Chongqing University, Chongqing 401331, China;
2 Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506, USA

收稿日期:2018-05-02 修回日期:2018-09-26 出版日期:2018-12-05 发布日期:2018-12-05
通讯作者: Ruchuan Liu, Guigen Zhang E-mail:phyliurc@cqu.edu.cn;guigen.bme@uky.edu
基金资助:
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).

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

Received:2018-05-02 Revised:2018-09-26 Online:2018-12-05 Published:2018-12-05
Contact: Ruchuan Liu, Guigen Zhang E-mail:phyliurc@cqu.edu.cn;guigen.bme@uky.edu
Supported by:
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).

摘要/Abstract

摘要：

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.

关键词: microfluidics, core-shell scaffold, phase field method, tumor spheroids

Abstract:

Key words: microfluidics, core-shell scaffold, phase field method, tumor spheroids

中图分类号: (Biophysical techniques (research methods))

87.80.-y

87.64.Aa (Computer simulation)

李岳南, 海苗苗, 赵宇, 吕亚蕾, 何益, 陈果, 刘雳宇, 刘如川, Guigen Zhang. Controlled generation of cell-laden hydrogel microspheres with core-shell scaffold mimicking microenvironment of tumor[J]. 中国物理B, 2018, 27(12): 128703-128703.

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[J]. Chin. Phys. B, 2018, 27(12): 128703-128703.

参考文献 41

[1]	Chen W, Zheng R, Baade P D, Zhang S, Zeng H, Bray F, Jemal A, Yu X Q and He J 2016 CA Cancer J. Clin. 66 115 doi: 10.3322/caac.21338
[2]	Grolman J M, Zhang D, Smith A M, Moore J S and Kilian K A 2015 Adv. Mater. 27 5512 doi: 10.1002/adma.201501729
[3]	Kim T G, Shin H and Lim D W 2012 Adv. Funct. Mater. 22 2446 doi: 10.1002/adfm.201103083
[4]	Truong D, Puleo J, Llave A, Mouneimne G, Kamm R D and Nikkhah M 2016 Sci. Rep. 6 34094 doi: 10.1038/srep34094
[5]	Carvalho M P, Costa E C, Miguel S P and Correia I J 2016 Carbohydr Polym 150 139 doi: 10.1016/j.carbpol.2016.05.005
[6]	Lee J M, Mhawech-Fauceglia P, Lee N, Parsanian L C, Lin Y G, Gayther S A and Lawrenson K 2013 Lab Invest 93 528 doi: 10.1038/labinvest.2013.41
[7]	Quail D F and Joyce J A 2013 Nat. Medicine 19 1423 doi: 10.1038/nm.3394
[8]	Patil P U, D'Ambrosio J, Inge L J, Mason R W and Rajasekaran A K 2015 J. Cell Sci. 128 4366 doi: 10.1242/jcs.173518
[9]	Nabet B Y, Qiu Y, Shabason J E, Wu T J, Yoon T, Kim B C, Benci J L, DeMichele A M, Tchou J, Marcotrigiano J and Minn A J 2017 Cell 170 352 doi: 10.1016/j.cell.2017.06.031
[10]	Fennema E, Rivron N, Rouwkema J, Blitterswijk C V and Boer J D 2013 Trends Biotechnology 31 108 doi: 10.1016/j.tibtech.2012.12.003
[11]	Kelm J M, Timmins N E, Brown C J, Fussenegger M and Nielsen L K 2003 Biotechnology & BioEng. 83 173 doi: chnology
[12]	Tung Y C, Hsiao A Y, Allen S G, Torisawa Y S, Ho M and Takayama S 2011 Analyst 136 473 doi: 10.1039/C0AN00609B
[13]	Santini M T and Rainaldi G 1999 Pathobiology 67 148 doi: 10.1159/000028065
[14]	Vinci M, Gowan S, Boxall F, Patterson L, Zimmermann M, Court W, Lomas C, Mendiola M, Hardisson D and Eccles S A 2012 Bmc Biol. 10 29 doi: 10.1186/1741-7007-10-29
[15]	Yu L, Chen M C and Cheung K C 2010 Lab Chip 10 2424 doi: 10.1039/c004590j
[16]	Tumarkin E, Tzadu L, Csaszar E, Seo M, Zhang H, Lee A, Peerani R, Purpura K, Zandstra P W and Kumacheva E 2011 Integrative Biol. Quant. Biosci. From Nano Macro 3 653 doi: 10.1039/c1ib00002k
[17]	Velasco D, Tumarkin E and Kumacheva E 2012 Small 8 1633 doi: 10.1002/smll.201102464
[18]	Karoubi G, Ormiston M L, Stewart D J and Courtman D W 2009 Biomaterials 30 5445 doi: 10.1016/j.biomaterials.2009.06.035
[19]	Barron C and He J Q 2017 J. BioMater. Sci. Polym. Ed. 28 1245 doi: 10.1080/09205063.2017.1318030
[20]	Gruene M, Pflaum M, Deiwick A, Koch L, Schlie S, Unger C, Wilhelmi M, Haverich A and Chichkov B N 2011 Biofabrication 3 015005 doi: 10.1088/1758-5082/3/1/015005
[21]	Loozen L D, Wegman F, Öner F C, Dhert W J A and Alblas J 2013 J. Mater. Chem. B 1 6619 doi: 10.1039/c3tb21093f
[22]	Chen Q, Utech S, Chen D, Prodanovic R, Lin J M and Weitz D A 2016 Lab Chip 16 1346 doi: 10.1039/C6LC00231E
[23]	Yu L, Grist S M, Nasseri S S, Cheng E, Hwang Y C, Ni C and Cheung K C 2015 Biomicrofluidics 9 507
[24]	Han W, Chen S, Yuan W, Fan Q, Tian J, Wang X, Chen L, Zhang X, Wei W and Liu R 2016 Proc. Natl Acad. Sci. USA 113 11208 doi: 10.1073/pnas.1610347113
[25]	Dolega M E, Abeille F, PicolletD 'Hahan N and Gidrol X 2015 Biomaterials 52 347 doi: 10.1016/j.biomaterials.2015.02.042
[26]	Fridman R, Benton G, Aranoutova I, Kleinman H K and Bonfil R D 2012 Nat. Protocols 7 1138 doi: 10.1038/nprot.2012.053
[27]	Kleinman H K and Martin G R Seminars in Cancer Biology pp. 378-386
[28]	Walters B D and Stegemann J P 2014 Acta BioMater. 10 1488 doi: 10.1016/j.actbio.2013.08.038
[29]	Kleinman H K, Klebe R J and Martin G R 1981 J. Cell Biol. 88 473 doi: 10.1083/jcb.88.3.473
[30]	Utada A S, Lorenceau E, Link D R, Kaplan P D, Stone H A and Weitz D A 2005 Science 308 537 doi: 10.1126/science.1109164
[31]	Whitesides G M, Ostuni E, Takayama S, Jiang X and Ingber D E 2001 Annu. Rev. BioMed. Eng. 3 335 doi: 10.1146/annurev.bioeng.3.1.335
[32]	Younan Xia G M W 1998 Angew. Chem. Int. Ed. 37 23
[33]	Mazutis L, Gilbert J, Ung W L, Weitz D A, Griffiths A D and Heyman J A 2013 Nat. Protocals 8 870 doi: 10.1038/nprot.2013.046
[34]	Andersen T, Auk-Emblem P and Dornish M 2015 Microarrays (Basel) 4 133
[35]	Loscertales I G, Barrero A, Guerrero I, Cortijo R, Marquez M and Gañán-Calvo A M 2002 Science 295 1695 doi: 10.1126/science.1067595
[36]	Thorsen T, Roberts R W, Arnold F H and Quake S R 2001 Phys. Rev. Lett. 86 4163 doi: 10.1103/PhysRevLett.86.4163
[37]	Ingeson-Carlsson C, Martinez-Monleon A and Nilsson M 2015 Exp. Cell Res. 338 127 doi: 10.1016/j.yexcr.2015.08.003
[38]	Baroud C N, Gallaire F and Dangla R 2010 Lab A Chip 10 2032 doi: 10.1039/c001191f
[39]	Gwon S H, Yoon J, Seok H K, Oh K H and Sun J Y 2015 Macromol. Res. 23 1112 doi: 10.1007/s13233-015-3151-9
[40]	Yue P, Feng J J, Liu C and Shen J 2004 J. Fluid Mech. 515 293 doi: 10.1017/S0022112004000370
[41]	Utech S, Prodanovic R, Mao A S, Ostafe R, Mooney D J and Weitz D A 2015 Adv. Healthc Mater. 4 1628 doi: 10.1002/adhm.201500021

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

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

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