A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High Throughput

Cell encapsulation has been widely employed in cell therapy, characterization, and analysis, as well as many other biomedical applications. While droplet-based microfluidic technology is advantageous in cell microencapsulation because of its modularity, controllability, mild conditions, and easy ope...

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Main Authors: Si Da Ling, Zhiqiang Liu, Wenjun Ma, Zhuo Chen, Yanan Du, Jianhong Xu
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Biosensors
Subjects:
Online Access:https://www.mdpi.com/2079-6374/12/8/659
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author Si Da Ling
Zhiqiang Liu
Wenjun Ma
Zhuo Chen
Yanan Du
Jianhong Xu
author_facet Si Da Ling
Zhiqiang Liu
Wenjun Ma
Zhuo Chen
Yanan Du
Jianhong Xu
author_sort Si Da Ling
collection DOAJ
description Cell encapsulation has been widely employed in cell therapy, characterization, and analysis, as well as many other biomedical applications. While droplet-based microfluidic technology is advantageous in cell microencapsulation because of its modularity, controllability, mild conditions, and easy operation when compared to other state-of-art methods, it faces the dilemma between high throughput and monodispersity of generated cell-laden microdroplets. In addition, the lack of a biocompatible method of de-emulsification transferring cell-laden hydrogel from cytotoxic oil phase into cell culture medium also hurtles the practical application of microfluidic technology. Here, a novel step-T-junction microchannel was employed to encapsulate cells into monodisperse microspheres at the high-throughput jetting regime. An alginate–gelatin co-polymer system was employed to enable the microfluidic-based fabrication of cell-laden microgels with mild cross-linking conditions and great biocompatibility, notably for the process of de-emulsification. The mechanical properties of alginate-gelatin hydrogel, e.g., stiffness, stress–relaxation, and viscoelasticity, are fully adjustable in offering a 3D biomechanical microenvironment that is optimal for the specific encapsulated cell type. Finally, the encapsulation of HepG2 cells into monodisperse alginate–gelatin microgels with the novel microfluidic system and the subsequent cultivation proved the maintenance of the long-term viability, proliferation, and functionalities of encapsulated cells, indicating the promising potential of the as-designed system in tissue engineering and regenerative medicine.
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spelling doaj.art-21efefa1ecac4764aae0de6165b019c02023-11-30T23:17:27ZengMDPI AGBiosensors2079-63742022-08-0112865910.3390/bios12080659A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High ThroughputSi Da Ling0Zhiqiang Liu1Wenjun Ma2Zhuo Chen3Yanan Du4Jianhong Xu5The State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, ChinaDepartment of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences Tsinghua University, Beijing 100084, ChinaThe State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, ChinaThe State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, ChinaDepartment of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences Tsinghua University, Beijing 100084, ChinaThe State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, ChinaCell encapsulation has been widely employed in cell therapy, characterization, and analysis, as well as many other biomedical applications. While droplet-based microfluidic technology is advantageous in cell microencapsulation because of its modularity, controllability, mild conditions, and easy operation when compared to other state-of-art methods, it faces the dilemma between high throughput and monodispersity of generated cell-laden microdroplets. In addition, the lack of a biocompatible method of de-emulsification transferring cell-laden hydrogel from cytotoxic oil phase into cell culture medium also hurtles the practical application of microfluidic technology. Here, a novel step-T-junction microchannel was employed to encapsulate cells into monodisperse microspheres at the high-throughput jetting regime. An alginate–gelatin co-polymer system was employed to enable the microfluidic-based fabrication of cell-laden microgels with mild cross-linking conditions and great biocompatibility, notably for the process of de-emulsification. The mechanical properties of alginate-gelatin hydrogel, e.g., stiffness, stress–relaxation, and viscoelasticity, are fully adjustable in offering a 3D biomechanical microenvironment that is optimal for the specific encapsulated cell type. Finally, the encapsulation of HepG2 cells into monodisperse alginate–gelatin microgels with the novel microfluidic system and the subsequent cultivation proved the maintenance of the long-term viability, proliferation, and functionalities of encapsulated cells, indicating the promising potential of the as-designed system in tissue engineering and regenerative medicine.https://www.mdpi.com/2079-6374/12/8/659microdropletmicrofluidicsmodified step-T-junctionviscoelasticitycell encapsulation
spellingShingle Si Da Ling
Zhiqiang Liu
Wenjun Ma
Zhuo Chen
Yanan Du
Jianhong Xu
A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High Throughput
Biosensors
microdroplet
microfluidics
modified step-T-junction
viscoelasticity
cell encapsulation
title A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High Throughput
title_full A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High Throughput
title_fullStr A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High Throughput
title_full_unstemmed A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High Throughput
title_short A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High Throughput
title_sort novel step t junction microchannel for the cell encapsulation in monodisperse alginate gelatin microspheres of varying mechanical properties at high throughput
topic microdroplet
microfluidics
modified step-T-junction
viscoelasticity
cell encapsulation
url https://www.mdpi.com/2079-6374/12/8/659
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