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Engineering Nanopatterned Structures to Orchestrate Macrophage Phenotype by Cell Shape.

Kai Li1, Lin Lv1, Dandan Shao1,2

  • 1Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China.

Journal of Functional Biomaterials
|March 24, 2022
PubMed
Summary

Surface nanotopographies instruct macrophage behavior. Small nanopillars and nanopits promote anti-inflammatory M2 phenotypes by influencing cell shape and activating specific signaling pathways, guiding biomaterial design for better immune response.

Keywords:
integrin β1macrophage cell shapenanopillarnanopitphenotype

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Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Immunology

Background:

  • Biomaterial surface topography influences macrophage behavior.
  • Nanopatterned surfaces offer opportunities to control the foreign body response.
  • Understanding macrophage mechanotransduction is key for biomaterial design.

Purpose of the Study:

  • To investigate RAW264.7 macrophage response to polydimethylsiloxane substrates with varying nanopillar and nanopit dimensions.
  • To correlate macrophage morphology and phenotype with specific nanotopography features.
  • To elucidate the role of integrin signaling and downstream pathways in mediating nanotopography-induced macrophage responses.

Main Methods:

  • Fabrication of polydimethylsiloxane substrates with controlled nanopillar (small and large) and nanopit features.
  • Culturing RAW264.7 macrophages on these substrates and a flat control.
  • Analysis of macrophage morphology, cell spreading, and elongation using microscopy.
  • Assessment of macrophage phenotype markers (M2) and inflammatory cytokine expression.
  • Investigation of integrin β1 expression, focal adhesion formation, and activation of the PI3K/Akt and NF-κB pathways.

Main Results:

  • Small nanopillars (SNPLs) induced well-spread macrophage morphology, while nanopits (NPTs) promoted cell elongation.
  • Both SNPLs and NPTs enhanced anti-inflammatory/pro-healing (M2) markers and downregulated inflammatory cytokines.
  • Nanotopographies facilitated integrin β1 expression and focal adhesion formation.
  • Integrin β1 activation of the PI3K/Akt pathway promoted cell spreading and inhibited NF-κB activation.

Conclusions:

  • Surface nanotopography is a critical factor in dictating macrophage cell shape and phenotype.
  • Specific nanopatterns can instruct macrophages towards an anti-inflammatory M2 phenotype.
  • Integrin-mediated signaling pathways are essential for translating physical cues from nanotopography into cellular responses, offering a design strategy for immune-instructive biomaterials.