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Viscoelastic hydrogels for interrogating pancreatic cancer-stromal cell interactions
Fang-Yi Lin1, Chun-Yi Chang2, Han Nguyen2
1Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA.
Materials Today. Bio
|February 23, 2023
Summary
This study developed a new biomimetic hydrogel to investigate matrix viscoelasticity's impact on pancreatic cancer cells. The findings reveal that viscoelasticity influences cancer cell behavior and the tumor microenvironment, offering new avenues for research.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Biophysics
Background:
- The tumor microenvironment (TME) significantly influences cancer progression and drug resistance.
- The role of matrix viscoelasticity in pancreatic cancer and its TME is largely unexplored.
- Existing tumor models do not fully capture the complex mechanical properties of the TME.
Purpose of the Study:
- To synthesize a novel biomimetic hydrogel with tunable viscoelastic properties.
- To investigate the effects of matrix viscoelasticity on pancreatic cancer cell (PCC) behavior in vitro.
- To provide an engineered platform for studying the TME.
Main Methods:
- Synthesis of phenylboronic acid-containing polymers (PEHA) via RAFT polymerization.
- Modification of PEHA with norbornene groups to create dual-functional PEHNBA polymers.
- Utilizing orthogonal photopolymerization and boronate ester complexation for tunable elasticity and stress-relaxation.
- In vitro encapsulation of PCCs and cancer-associated fibroblasts (CAFs) within the hydrogels.
Main Results:
- PEHNBA polymers demonstrated high cytocompatibility for cell encapsulation.
- Hydrogels with high stress-relaxation promoted CAF spreading, enhancing PCC proliferation and spreading.
- Viscoelastic matrices upregulated the secretion of proteins associated with epithelial-mesenchymal transition (EMT).
Conclusions:
- Matrix viscoelasticity plays a crucial role in determining pancreatic cancer cell fate.
- The developed engineered viscoelastic matrix is a valuable tool for TME research.
- This study highlights the importance of mechanical properties in cancer progression and therapeutic resistance.
