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Tumor Spheroid Fabrication and Encapsulation in Polyethylene Glycol Hydrogels for Studying Spheroid-Matrix Interactions
Published on: September 22, 2023
A cell-instructive hydrogel to regulate malignancy of 3D tumor spheroids with matrix rigidity
Youyun Liang1, Jaehyun Jeong, Ross J DeVolder
1Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA.
Biomaterials
|September 14, 2011
Summary
This study shows that matrix stiffness influences cancer cell behavior in 3D tumor spheroids. Softer gels promote malignancy, while stiffer gels suppress it, offering new insights for cancer research.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Materials Science
Background:
- Three dimensional (3D) tumor spheroid models are crucial for cancer research.
- Current models lack the ability to represent varying cancer malignancy levels.
- Hydrogel mechanical rigidity affects cancer cell phenotypes, suggesting a role in 3D spheroid malignancy.
Purpose of the Study:
- To develop 3D liver tumor spheroids with controlled organization, phenotypes, and angiogenic activity.
- To investigate the role of matrix stiffness in 3D tumor spheroid malignancy, independent of permeability.
- To create advanced hydrogel models for cancer studies.
Main Methods:
- Assembled 3D liver tumor spheroids using hydrogels with tunable stiffness.
- Modified collagen gel stiffness by altering poly(ethylene glycol) di-(succinic acid N-hydroxysuccinimidyl ester) content.
- Controlled intercellular organization, phenotypes, and angiogenic activities.
Main Results:
- Hepatocellular carcinoma cells in softer, fat-like hydrogels formed malignant spheroids.
- Cells in stiffer, liver-like hydrogels formed compact hepatoids with suppressed malignancy.
- Developed hydrogels with controlled stiffness and minimal changes in molecular diffusivity.
Conclusions:
- Matrix stiffness significantly modulates the malignancy of 3D tumor spheroids.
- The developed hydrogel and spheroid models are valuable tools for understanding and regulating cancer cell behavior.
- This research provides a new platform for studying cancer malignancy in a 3D context.
