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.
|
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
|
[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
|
[2] |
Grolman J M, Zhang D, Smith A M, Moore J S and Kilian K A 2015 Adv. Mater. 27 5512
|
[3] |
Kim T G, Shin H and Lim D W 2012 Adv. Funct. Mater. 22 2446
|
[4] |
Truong D, Puleo J, Llave A, Mouneimne G, Kamm R D and Nikkhah M 2016 Sci. Rep. 6 34094
|
[5] |
Carvalho M P, Costa E C, Miguel S P and Correia I J 2016 Carbohydr Polym 150 139
|
[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
|
[7] |
Quail D F and Joyce J A 2013 Nat. Medicine 19 1423
|
[8] |
Patil P U, D'Ambrosio J, Inge L J, Mason R W and Rajasekaran A K 2015 J. Cell Sci. 128 4366
|
[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
|
[10] |
Fennema E, Rivron N, Rouwkema J, Blitterswijk C V and Boer J D 2013 Trends Biotechnology 31 108
|
[11] |
Kelm J M, Timmins N E, Brown C J, Fussenegger M and Nielsen L K 2003 Biotechnology & BioEng. 83 173
|
[12] |
Tung Y C, Hsiao A Y, Allen S G, Torisawa Y S, Ho M and Takayama S 2011 Analyst 136 473
|
[13] |
Santini M T and Rainaldi G 1999 Pathobiology 67 148
|
[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
|
[15] |
Yu L, Chen M C and Cheung K C 2010 Lab Chip 10 2424
|
[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
|
[17] |
Velasco D, Tumarkin E and Kumacheva E 2012 Small 8 1633
|
[18] |
Karoubi G, Ormiston M L, Stewart D J and Courtman D W 2009 Biomaterials 30 5445
|
[19] |
Barron C and He J Q 2017 J. BioMater. Sci. Polym. Ed. 28 1245
|
[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
|
[21] |
Loozen L D, Wegman F, Öner F C, Dhert W J A and Alblas J 2013 J. Mater. Chem. B 1 6619
|
[22] |
Chen Q, Utech S, Chen D, Prodanovic R, Lin J M and Weitz D A 2016 Lab Chip 16 1346
|
[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
|
[25] |
Dolega M E, Abeille F, PicolletD 'Hahan N and Gidrol X 2015 Biomaterials 52 347
|
[26] |
Fridman R, Benton G, Aranoutova I, Kleinman H K and Bonfil R D 2012 Nat. Protocols 7 1138
|
[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
|
[29] |
Kleinman H K, Klebe R J and Martin G R 1981 J. Cell Biol. 88 473
|
[30] |
Utada A S, Lorenceau E, Link D R, Kaplan P D, Stone H A and Weitz D A 2005 Science 308 537
|
[31] |
Whitesides G M, Ostuni E, Takayama S, Jiang X and Ingber D E 2001 Annu. Rev. BioMed. Eng. 3 335
|
[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
|
[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
|
[36] |
Thorsen T, Roberts R W, Arnold F H and Quake S R 2001 Phys. Rev. Lett. 86 4163
|
[37] |
Ingeson-Carlsson C, Martinez-Monleon A and Nilsson M 2015 Exp. Cell Res. 338 127
|
[38] |
Baroud C N, Gallaire F and Dangla R 2010 Lab A Chip 10 2032
|
[39] |
Gwon S H, Yoon J, Seok H K, Oh K H and Sun J Y 2015 Macromol. Res. 23 1112
|
[40] |
Yue P, Feng J J, Liu C and Shen J 2004 J. Fluid Mech. 515 293
|
[41] |
Utech S, Prodanovic R, Mao A S, Ostafe R, Mooney D J and Weitz D A 2015 Adv. Healthc Mater. 4 1628
|
No Suggested Reading articles found! |
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
Altmetric
|
blogs
Facebook pages
Wikipedia page
Google+ users
|
Online attention
Altmetric calculates a score based on the online attention an article receives. Each coloured thread in the circle represents a different type of online attention. The number in the centre is the Altmetric score. Social media and mainstream news media are the main sources that calculate the score. Reference managers such as Mendeley are also tracked but do not contribute to the score. Older articles often score higher because they have had more time to get noticed. To account for this, Altmetric has included the context data for other articles of a similar age.
View more on Altmetrics
|
|
|