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Micropatterning and Assembly of 3D Microvessels
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Engineered microenvironments for synergistic VEGF - Integrin signalling during vascularization.

Vladimíra Moulisová1, Cristina Gonzalez-García1, Marco Cantini1

  • 1Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, United Kingdom.

Biomaterials
|March 11, 2017
PubMed
Summary
This summary is machine-generated.

Engineered polymer microenvironments promote blood vessel formation by organizing fibronectin (FN) to enhance integrin and vascular endothelial growth factor (VEGF) signaling, improving vasculogenesis in vitro and in vivo.

Keywords:
FibronectinGrowth factorsProtein assemblyVEGFVascularizationpoly(ethyl acrylate)

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Cell Signaling

Background:

  • Vasculogenesis, the formation of new blood vessels, is crucial for tissue regeneration.
  • Current methods often require high growth factor concentrations and lack synergistic signaling.
  • Integrin and growth factor receptor signaling pathways play key roles in endothelial cell function.

Purpose of the Study:

  • To engineer polymer-based microenvironments that promote vasculogenesis via synergistic integrin-growth factor receptor signaling.
  • To investigate the role of fibronectin (FN) organization on poly(ethyl acrylate) (PEA) in enhancing vascular endothelial growth factor (VEGF) presentation and signaling.
  • To evaluate the efficacy of this material platform for promoting vascularization in vitro and in vivo.

Main Methods:

  • Fabrication of polymer microenvironments using poly(ethyl acrylate) (PEA) and poly(methyl acrylate) (PMA) as controls.
  • Characterization of fibronectin (FN) organization and binding domains on polymer surfaces.
  • In vitro studies using human endothelial cells to assess cell response, signaling pathway activation (PLCγ1, ERK1/2 phosphorylation), and vasculogenesis.
  • In vivo studies using 3D scaffolds in murine models to evaluate vascularization.

Main Results:

  • PEA induced spontaneous organization of FN into nanonetworks, simultaneously presenting integrin and growth factor binding domains.
  • Synergistic integrin/VEGF signaling was enhanced on PEA, leading to improved vasculogenesis in vitro with lower VEGF concentrations.
  • VEGF specifically bound to FN fibrils on PEA, unlike control polymers, and promoted early signaling events (PLCγ1, ERK1/2 phosphorylation).
  • In vivo implantation of FN/VEGF-coated PEA scaffolds demonstrated enhanced vascularization and tissue formation.

Conclusions:

  • Polymer-driven FN organization on PEA creates synergistic signaling interfaces that effectively promote vasculogenesis.
  • This material platform enhances endothelial cell response and vascularization through combined integrin and VEGF signaling.
  • The engineered microenvironment holds promise for regenerative medicine applications requiring enhanced vascularization.