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Macrophage Phenotypic Changes on FN-Coated Physical Gradient Hydrogels.

Zhuqing Li1, Kaitlin M Bratlie1,2

  • 1Department of Materials Science & Engineering, Iowa State University, Ames, Iowa 50011, United States.

ACS Applied Bio Materials
|January 10, 2022
PubMed
Summary

Tissue scaffold stiffness and fibronectin coating influence macrophage behavior. Mechanical gradients can control macrophage polarization, crucial for tissue engineering and healing.

Keywords:
fibronectingellan gum hydrogelmacrophage polarizationphotopolymerizationstiffness gradient

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Area of Science:

  • Biomaterials Science
  • Cellular Biology
  • Tissue Engineering

Background:

  • Tissue engineering scaffolds require precise chemical and physical properties to mimic living tissues.
  • Macrophages are key immune cells that respond to microenvironmental cues, influencing tissue healing and immune responses.
  • Spatiotemporal gradients in physical or chemical signals can modulate macrophage behavior, including polarization, proliferation, and adhesion.

Purpose of the Study:

  • To investigate macrophage phenotypic changes on methacrylated gellan gum hydrogels with varying stiffnesses (5-30 kPa).
  • To evaluate the effects of fibronectin (FN) coating on macrophage behavior and polarization on these hydrogels.
  • To explore the potential of mechanical gradients in controlling macrophage polarization for tissue engineering applications.

Main Methods:

  • Macrophages (classically M1 and alternatively M2 activated) were cultured on untreated and FN-coated methacrylated gellan gum hydrogels of varying compressive moduli.
  • Macrophage proliferation, adhesion, spreading, and polarization (assessed via urea/nitrite ratio and arginine activity/CD206 expression) were analyzed.
  • The influence of mechanical gradients on macrophage polarization was examined by culturing cells on adjacent gels of different stiffnesses.

Main Results:

  • FN coating increased macrophage proliferation and spreading on the hydrogels.
  • Untreated rigid substrates promoted a pro-inflammatory phenotype in both M1 and M2 macrophages.
  • FN-coated stiffer gels induced an anti-inflammatory phenotype in M2 macrophages, while M1 polarization was unaffected.
  • Macrophage polarization was not influenced by neighboring cells on gels with different stiffnesses.

Conclusions:

  • Mechanical stiffness and fibronectin presence are critical factors modulating macrophage polarization.
  • Fibronectin coating can steer M2 macrophage polarization towards an anti-inflammatory state on stiffer substrates.
  • Utilizing mechanical gradients offers a promising strategy for controlling macrophage responses in tissue engineering and promoting proper wound healing.