Synergistic Approach of High-Precision 3D Printing and Low Cell Adhesion for Enhanced Self-Assembled Spheroid Formation

Spheroids, as three-dimensional (3D) cell aggregates, can be prepared using various methods, including hanging drops, microwells, microfluidics, magnetic manipulation, and bioreactors. However, current spheroid manufacturing techniques face challenges such as complex workflows, the need for speciali...

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Main Authors: Chunxiang Lu, Aoxiang Jin, Chuang Gao, Hao Qiao, Huazhen Liu, Yi Zhang, Wenbin Sun, Shih-Mo Yang, Yuanyuan Liu
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biosensors
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Online Access:https://www.mdpi.com/2079-6374/15/1/7
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author Chunxiang Lu
Aoxiang Jin
Chuang Gao
Hao Qiao
Huazhen Liu
Yi Zhang
Wenbin Sun
Shih-Mo Yang
Yuanyuan Liu
author_facet Chunxiang Lu
Aoxiang Jin
Chuang Gao
Hao Qiao
Huazhen Liu
Yi Zhang
Wenbin Sun
Shih-Mo Yang
Yuanyuan Liu
author_sort Chunxiang Lu
collection DOAJ
description Spheroids, as three-dimensional (3D) cell aggregates, can be prepared using various methods, including hanging drops, microwells, microfluidics, magnetic manipulation, and bioreactors. However, current spheroid manufacturing techniques face challenges such as complex workflows, the need for specialized personnel, and poor batch reproducibility. In this study, we designed a support-free, 3D-printed microwell chip and developed a compatible low-cell-adhesion process. Through simulation and experimental validation, we rapidly optimized microwell size and the coating process. We successfully formed three types of spheroids—human immortalized epidermal cells (HaCaTs), umbilical cord mesenchymal stem cells (UC-MSCs), and human osteosarcoma cells (MG63s)—on the chip. Fluorescent viability staining confirmed the biocompatibility and reliability of the chip. Finally, drug response experiments were conducted using the chip. Compared to traditional methods, our proposed strategy enables high-throughput production of size-controlled spheroids with excellent shape retention, while enhanced gas exchange during culture improves differentiation marker expression. This platform provides an efficient and cost-effective solution for biosensing applications, such as drug screening, disease modeling, and personalized therapy monitoring. Furthermore, the chip shows significant potential for real-time in vitro monitoring of cellular viability, reaction kinetics, and drug sensitivity, offering valuable advancements in biosensor technology for life sciences and medical applications.
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series Biosensors
spelling doaj-art-264a1e70e144437ca2c3464b94ea3e422025-01-24T13:25:24ZengMDPI AGBiosensors2079-63742024-12-01151710.3390/bios15010007Synergistic Approach of High-Precision 3D Printing and Low Cell Adhesion for Enhanced Self-Assembled Spheroid FormationChunxiang Lu0Aoxiang Jin1Chuang Gao2Hao Qiao3Huazhen Liu4Yi Zhang5Wenbin Sun6Shih-Mo Yang7Yuanyuan Liu8School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, ChinaSchool of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, ChinaSchool of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, ChinaSchool of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, ChinaSchool of Medicine, Shanghai University, Shanghai 200444, ChinaSchool of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, ChinaSchool of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, ChinaSchool of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, ChinaSchool of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, ChinaSpheroids, as three-dimensional (3D) cell aggregates, can be prepared using various methods, including hanging drops, microwells, microfluidics, magnetic manipulation, and bioreactors. However, current spheroid manufacturing techniques face challenges such as complex workflows, the need for specialized personnel, and poor batch reproducibility. In this study, we designed a support-free, 3D-printed microwell chip and developed a compatible low-cell-adhesion process. Through simulation and experimental validation, we rapidly optimized microwell size and the coating process. We successfully formed three types of spheroids—human immortalized epidermal cells (HaCaTs), umbilical cord mesenchymal stem cells (UC-MSCs), and human osteosarcoma cells (MG63s)—on the chip. Fluorescent viability staining confirmed the biocompatibility and reliability of the chip. Finally, drug response experiments were conducted using the chip. Compared to traditional methods, our proposed strategy enables high-throughput production of size-controlled spheroids with excellent shape retention, while enhanced gas exchange during culture improves differentiation marker expression. This platform provides an efficient and cost-effective solution for biosensing applications, such as drug screening, disease modeling, and personalized therapy monitoring. Furthermore, the chip shows significant potential for real-time in vitro monitoring of cellular viability, reaction kinetics, and drug sensitivity, offering valuable advancements in biosensor technology for life sciences and medical applications.https://www.mdpi.com/2079-6374/15/1/7biofabrication3D printingchipspheroid
spellingShingle Chunxiang Lu
Aoxiang Jin
Chuang Gao
Hao Qiao
Huazhen Liu
Yi Zhang
Wenbin Sun
Shih-Mo Yang
Yuanyuan Liu
Synergistic Approach of High-Precision 3D Printing and Low Cell Adhesion for Enhanced Self-Assembled Spheroid Formation
Biosensors
biofabrication
3D printing
chip
spheroid
title Synergistic Approach of High-Precision 3D Printing and Low Cell Adhesion for Enhanced Self-Assembled Spheroid Formation
title_full Synergistic Approach of High-Precision 3D Printing and Low Cell Adhesion for Enhanced Self-Assembled Spheroid Formation
title_fullStr Synergistic Approach of High-Precision 3D Printing and Low Cell Adhesion for Enhanced Self-Assembled Spheroid Formation
title_full_unstemmed Synergistic Approach of High-Precision 3D Printing and Low Cell Adhesion for Enhanced Self-Assembled Spheroid Formation
title_short Synergistic Approach of High-Precision 3D Printing and Low Cell Adhesion for Enhanced Self-Assembled Spheroid Formation
title_sort synergistic approach of high precision 3d printing and low cell adhesion for enhanced self assembled spheroid formation
topic biofabrication
3D printing
chip
spheroid
url https://www.mdpi.com/2079-6374/15/1/7
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