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Modulating Neutrophil Extracellular Trap Formation In Vivo with Locoregional Precision Using Differently Charged

Tania L Lopez-Silva1, Caleb F Anderson1, Joel P Schneider1

  • 1Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, United States.

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|March 31, 2025
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Summary

Charged peptide hydrogels can control the release of neutrophil extracellular traps (NETs), which are DNA networks involved in inflammation. Positively charged gels promote NET formation, while negatively charged ones do not, offering tunable control.

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Area of Science:

  • Biomaterials Science
  • Immunology
  • Tissue Engineering

Background:

  • Neutrophil extracellular traps (NETs) are DNA networks released by neutrophils.
  • Initially identified as a defense mechanism against pathogens, NETs are now implicated in various inflammatory diseases.
  • Physical properties of materials can influence NET formation.

Purpose of the Study:

  • To investigate the impact of peptide hydrogel charge on NET formation in vivo.
  • To determine if tunable control over NET formation is achievable using self-assembled peptide hydrogels.
  • To explore the potential of this material platform for modulating inflammatory responses.

Main Methods:

  • Fabrication of self-assembled peptide hydrogels with varying surface charges (positive and negative).
  • Implantation of hydrogels in vivo to assess host immune response.
  • Quantification of NET formation using established assays.

Main Results:

  • Positively charged peptide hydrogels significantly induced rapid NET formation.
  • Negatively charged peptide hydrogels did not promote NET release.
  • The charge-dependent immune response allowed for predictable, rheostat-like modulation of NET formation.

Conclusions:

  • The surface charge of self-assembled peptide hydrogels is a critical determinant of NET formation in vivo.
  • This discovery enables the development of a novel material platform for precise control over NET formation.
  • This platform holds potential for therapeutic strategies targeting inflammatory diseases.