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A "sandwich" cell culture platform with NIR-responsive dynamic stiffness to modulate macrophage phenotypes
Peiqi Yuan1, Yilun Luo, Yu Luo
1MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. liema@zju.edu.cn.
Biomaterials Science
|February 12, 2021
Summary
Researchers developed a novel biomaterial that dynamically changes stiffness using near-infrared light. This allows for in situ control of macrophage phenotypes, crucial for tissue repair and immune therapy.
Area of Science:
- Biomaterials Science
- Immunology
- Tissue Engineering
Background:
- Macrophages play critical roles in tissue repair and immune responses.
- Controlling macrophage phenotypes is a promising strategy for therapeutic applications.
- Existing methods often rely on cytokine stimuli, which can be invasive.
Purpose of the Study:
- To develop a novel cell culture platform with tunable stiffness for in situ macrophage polarization.
- To investigate the dynamic relationship between substrate stiffness and macrophage phenotype.
- To establish a non-cytokine-based method for modulating immune reactions.
Main Methods:
- Fabrication of a "sandwich" cell culture platform with near-infrared (NIR) responsive dynamic stiffness.
- Utilizing IR780-mixed phase change material (PCM) and hyaluronic acid-sodium alginate hydrogel (MA-HA&SA).
- NIR irradiation to induce photothermal effect, calcium ion diffusion, and hydrogel crosslinking, increasing stiffness.
- Quantification of macrophage phenotypes using immunostaining for inducible nitric oxide synthase (iNOS) and enzyme-linked immune sorbent assay (ELISA) for tumor necrosis factor-α (TNF-α).
- Assessment of nuclear Yes-associated-protein (YAP) ratio.
Main Results:
- NIR irradiation successfully increased hydrogel stiffness in situ.
- Macrophages transformed from an anti-inflammatory to a pro-inflammatory phenotype under dynamic stiffness.
- Up-regulation of iNOS and TNF-α confirmed the phenotypic shift.
- Nuclear YAP ratio positively correlated with the observed macrophage phenotype shift.
Conclusions:
- The developed biomaterial platform enables dynamic, non-cytokine-mediated modulation of macrophage phenotypes.
- This approach offers an effective and non-invasive strategy to manipulate immune reactions for optimized healing and therapeutic outcomes.
- The study highlights the critical role of substrate stiffness in dictating macrophage behavior.
