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Microfluidic Fabrication of Core-Shell Microcapsules carrying Human Pluripotent Stem Cell Spheroids
Published on: October 13, 2021
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Mild formation of core-shell hydrogel microcapsules for cell encapsulation.
Zeyang Liu1,2,3, Hongyong Zhang2,3, Zhen Zhan2
1Stem Cell Therapy and Regenerative Medicine Lab, Tsinghua-Berkeley Shenzhen Institute (TBSI), No.1001 Xueyuan Avenue, Nanshan District, Shenzhen, People's Republic of China.
Biofabrication
|December 3, 2020
Summary
This study introduces an improved internal gelation method for creating robust core-shell hydrogel microcapsules. The new technique enhances mechanical stability and cell survival rates for applications in drug delivery and tissue regeneration.
Area of Science:
- Biomaterials Science
- Chemical Engineering
- Regenerative Medicine
Background:
- Internal gelation is a key sol-gel method for microgel preparation, but often yields microgels with poor mechanical stability and low cell viability.
- Existing methods struggle with irregular surface morphology and insufficient cell survival rates, limiting applications in drug delivery and cell therapy.
Purpose of the Study:
- To develop an improved internal gelation approach for producing core-shell hydrogel microcapsules with enhanced mechanical stability, smooth surfaces, and high cell survival rates.
- To create microcapsules suitable for advanced applications like drug delivery, cell therapy, and tissue regeneration.
Main Methods:
- Utilized a coaxial flow-focusing microfluidic device for precise control over microcapsule formation.
- Employed alginate for the hydrogel shell, leveraging its rapid gelling properties for well-defined structures.
- Incorporated 2-[4-(2-Hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES) in the shell stream to buffer acidity during crosslinking, ensuring cell viability.
Main Results:
- Successfully prepared core-shell hydrogel microcapsules (200-600 μm) with smooth surfaces and significantly improved mechanical stability.
- Achieved high cell survival rates for encapsulated HepG2 cells and 3T3 fibroblasts in a co-culture setting.
- Demonstrated that the mild gelation conditions preserve cell viability and functionality.
Conclusions:
- The enhanced internal gelation method offers a robust platform for generating high-quality hydrogel microcapsules.
- This technique overcomes limitations of previous methods, enabling effective cell encapsulation and supporting applications in regenerative medicine and drug delivery.
- The developed microcapsules show promise for advanced biomedical applications requiring stable, biocompatible structures.

