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Hydrogel arrays formed via differential wettability patterning enable combinatorial screening of stem cell behavior
Ngoc Nhi T Le1, Stefan Zorn2, Samantha K Schmitt1
1Materials Science Program, University of Wisconsin-Madison, Madison, WI, USA.
Acta Biomaterialia
|September 20, 2015
Summary
We developed a novel hydrogel array method for high-throughput screening of cell behavior. This technique allows for easy screening of substrate stiffness and cell adhesion peptide concentration, revealing synergistic effects on human mesenchymal stem cell (hMSC) proliferation.
Area of Science:
- Biomaterials Science
- Stem Cell Biology
- Cellular Mechanosensing
Background:
- High-throughput screening of cell behavior requires controlled microenvironments.
- Understanding stem cell responses to substrate properties is crucial for regenerative medicine.
- Current methods for creating cell culture arrays can be complex and require specialized equipment.
Purpose of the Study:
- To develop a novel, benchtop method for forming hydrogel arrays for enhanced-throughput screening.
- To investigate the combinatorial effects of substrate stiffness and cell adhesion peptide concentration on human mesenchymal stem cell (hMSC) behavior.
- To demonstrate the utility of these arrays for studying cell response to combined biochemical and biophysical cues.
Main Methods:
- Fabrication of hydrogel arrays using surfaces patterned with differential wettability.
- Combinatorial screening of substrate stiffness and immobilized CRGDS peptide concentration.
- 2D cell culture of hMSCs on the fabricated hydrogel arrays.
- Analysis of hMSC initial attachment, spreading, proliferation, and mechanosensing.
Main Results:
- hMSC attachment, spreading, and proliferation linearly correlated with CRGDS peptide concentration, irrespective of stiffness.
- Increased substrate stiffness also enhanced hMSC attachment, spreading, and proliferation.
- Synergistic effects between CRGDS peptide concentration and substrate stiffness were observed, influencing hMSC behavior.
- Maximal hMSC proliferation occurred at high stiffness or high peptide concentration, suggesting a requirement for cytoskeletal tension.
Conclusions:
- A novel, liquid-handling-free method for benchtop hydrogel array formation was developed.
- These hydrogel arrays enable high-throughput screening of chemical and physical substrate properties on stem cell behavior.
- Synergy between cell adhesion and mechanosensing signals can be engineered to regulate hMSC behavior.
- The method is compatible with existing microarray systems for simultaneous control of the cellular environment.
