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Generation of Multicue Cellular Microenvironments by UV-Photopatterning of Three-Dimensional Cell Culture Substrates
Published on: June 2, 2022
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Dynamic cell patterning and photopolymerization with electric field modulation for constructing hierarchical tumor
Anping Wu1, Yanfeng Zhao2, Xinyi Dong2
1Intelligent Robotics Institute, School of Mechatronics Engineering, Beijing Institute of Technology, Beijing 100081, China; School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China.
Acta Biomaterialia
|November 15, 2025
Summary
This study presents a novel 3D bioprinting method to create advanced tumor models. The technique uses electric fields and UV light to assemble viable tumor spheroids within engineered extracellular matrix (ECM) environments for better cancer research.
Area of Science:
- Biotechnology
- Biomedical Engineering
- Cancer Research
Background:
- Tumor spheroids are valuable in vitro models for studying cancer pathophysiology.
- Existing tumor spheroids often fail to replicate the complex tumor microenvironment (TME) due to limitations in mimicking cell-cell and cell-extracellular matrix (ECM) interactions.
- Reconstructing a hierarchical TME requires precise spatial organization of cells and ECM components, which is challenging in current bioprinting methods.
Purpose of the Study:
- To develop a versatile strategy for assembling tumor spheroids and constructing individualized ECM-mimicking environments.
- To create more accurate in vitro models that replicate the native hierarchical TME.
- To provide a controllable platform for drug discovery and cancer research.
Main Methods:
- Utilized a uniform electric field to modulate hydrogel droplet wettability for precise positioning.
- Employed dielectrophoresis (DEP) induced by a non-uniform electric field to guide cell aggregation into patterned tumor spheroids.
- Integrated a digital micromirror device (DMD) to control UV patterns for photopolymerization and precise encapsulation of spheroids, forming tumor models.
Main Results:
- Successfully aggregated breast and liver cancer cells into tumor spheroids with high viability, proliferative capacity, and morphological regularity (circularity 0.84).
- Demonstrated increased invasiveness (approx. 77%) of liver cancer spheroids when encapsulated in hydrogels containing endothelial cells.
- Showcased the formation of compact, viable, and uniform tumor spheroids within customizable, biomimetic TMEs.
Conclusions:
- The proposed multifunctional strategy integrates dielectrophoretic droplet manipulation with 3D bioprinting for precise TME reconstruction.
- This approach enables the formation of advanced tumor models that better mimic native tumor architecture and functionality.
- The developed platform offers unprecedented possibilities for future drug discovery, cancer research, and personalized medicine.
