Heterogeneous spheroids with tunable interior morphologies by droplet-based microfluidics

Zhan, Zhen; Liu, Zeyang; Nan, Haochen; Li, Jianjie; Xie, Yuan; Hu, Chengzhi

2022-04-01

10.1088/1758-5090/ac5e12

Biofabrication   影响因子和分区

1758-5082

1758-5090

Heterogeneous spheroids that mimic the complex three-dimensional environment of natural tissues are needed in various biomedical applications. Geometric cues from cellular matrix play invaluable roles in governing cell behavior and phenotype. However, the structural complexity of interior morphologies of spheroids is currently limited due to poor spatial resolution of positioning/orientation of cellular constructs. Here, a coaxial capillary microfluidic device is developed to generate gelatin methacrylate (GelMA) microspheres with tunable dimensions and interior morphologies, such as core-shell, or microspheres with interior undulated wavy, or spiral canals, by manipulating the two-phase flow of hydrogel precursor solution and methylcellulose solution. The formation of diverse and exquisite interior morphologies is caused by the interacting viscous instabilities of the two-phase flow in the microfluidic system, followed by water-in-oil emulsion and photo-initiated polymerization. Polyethylene glycol diacrylate (PEGDA) is incorporated into the GelMA solution to tune the mechanical properties of the fabricated microspheres, and an optimized concentration of PEGDA is confirmed by evaluating the in vitro proliferation and vascularization of human umbilical vein endothelial cells. Further, a heterogeneous spheroid with spiral blood vessel lumen is constructed to demonstrate the versatility and potential of the proposed droplet-based microfluidic approach for building functional tissue constructs.

microfluidics heterogeneous spheroids microenvironments tissue engineering viscous instability

SCI ; EI

英语

第一 ; 通讯

National Natural Science Foundation of China[61903177] ; Shenzhen Science and Technology Program[JCYJ20190809144013494] ; Science and Technology Program of Guangdong[2021A1515011813] ; Special Funds for the Cultivation of Guangdong College Students' Scientific and Technological Innovation ("Climbing Program" Special Funds)[pdjh2021c0050] ; Science, Technology and Innovation Commission of Shenzhen Municipality[ZDSYS20200811143601004]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000778384600001

IOP Publishing Ltd

20221712032559

Biomechanics ; Blood vessels ; Drops ; Emulsification ; Emulsions ; Endothelial cells ; Fluidic devices ; Medical applications ; Microspheres ; Tissue ; Tissue engineering ; Two phase flow

Biomedical Engineering:461.1 ; Biological Materials and Tissue Engineering:461.2 ; Biomechanics, Bionics and Biomimetics:461.3 ; Biology:461.9 ; Fluid Flow, General:631.1 ; Hydraulic Equipment and Machinery:632.2 ; Microfluidics:632.5.1 ; Control Equipment:732.1 ; Chemical Operations:802.3 ; Chemical Products Generally:804

Web of Science

Southern Univ Sci & Technol, Dept Mech & Energy Engn, Shenzhen Key Lab Biomimet Robot & Intelligent Sys, Shenzhen 518055, Peoples R China

Zhan, Zhen,Liu, Zeyang,Nan, Haochen,et al. Heterogeneous spheroids with tunable interior morphologies by droplet-based microfluidics[J]. Biofabrication,2022,14(2).

Zhan, Zhen,Liu, Zeyang,Nan, Haochen,Li, Jianjie,Xie, Yuan,&Hu, Chengzhi.(2022).Heterogeneous spheroids with tunable interior morphologies by droplet-based microfluidics.Biofabrication,14(2).

Zhan, Zhen,et al."Heterogeneous spheroids with tunable interior morphologies by droplet-based microfluidics".Biofabrication 14.2(2022).