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Hydrogel Network Dynamics Regulate Vascular Morphogenesis.

Zhao Wei1, Rahel Schnellmann1, Hawley C Pruitt1

  • 1Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology, Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA.

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Summary

Dynamic hydrogels promote cell contractility and vascular tissue formation by activating integrin signaling. This research highlights the crucial role of matrix dynamics in vascular morphogenesis and tissue engineering.

Keywords:
cell contractilityintegrin clusteringstress-relaxationvasculogenesis

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Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Tissue Engineering

Background:

  • Matrix dynamics significantly influence multicellular tissue development.
  • Understanding vascular morphogenesis requires investigating cell-matrix interactions.

Purpose of the Study:

  • To investigate mechanisms of vascular morphogenesis using hydrogels with varying crosslinking capacities.
  • To elucidate the role of matrix dynamics in endothelial cell behavior and tissue formation.

Main Methods:

  • Development of dynamic (D) and non-dynamic (N) hydrogels with identical polymer components.
  • Assessment of human endothelial colony-forming cells (hECFCs) contractility, integrin clustering, and focal adhesion kinase (FAK) signaling.
  • In vitro and in vivo evaluation of vascular assembly and angiogenesis.

Main Results:

  • Dynamic hydrogels enhanced hECFC contractility, integrin β1 clustering, and FAK signaling, leading to robust vasculature assembly.
  • Non-dynamic hydrogels and stiff hydrogels (both D and N) did not promote FAK signaling or vascular morphogenesis.
  • Dynamic hydrogels promoted microvessel formation and angiogenesis in vivo.

Conclusions:

  • Cell contractility mediates integrin signaling through inside-out signaling pathways.
  • Matrix dynamics are critical for vascular tissue formation, impacting cell signaling and morphogenesis.
  • Findings inform future vascularization and tissue engineering strategies.