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Engineering 3D Cellularized Collagen Gels for Vascular Tissue Regeneration
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Collagen I hydrogel microstructure and composition conjointly regulate vascular network formation.

Michael G McCoy1, Bo Ri Seo1, Siyoung Choi1

  • 1Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, United States.

Acta Biomaterialia
|August 23, 2016
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Controlling collagen microstructure and Matrigel composition in 3D cultures influences vascular network formation. This research impacts understanding of neovascularization and tissue engineering.

Keywords:
Endothelial cellsExtracellular matrixInterleukin-8MicroenvironmentVascularization

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Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Tissue Engineering

Background:

  • Neovascularization, or new blood vessel formation, is crucial for tissue remodeling in both health and disease.
  • The extracellular matrix (ECM) plays a significant role in regulating neovascularization.
  • Existing in vitro models using collagen I or Matrigel alone do not fully replicate the in vivo ECM's complex influence on endothelial cells.

Purpose of the Study:

  • To investigate how controlled variations in collagen I microstructure and Matrigel composition within 3D hydrogel models affect vascular network formation.
  • To elucidate the mechanisms by which ECM structure and composition influence human cerebral microvascular endothelial cell (hCMEC) behavior and vascular development.

Main Methods:

  • Utilized microfabricated 3D culture systems to precisely control collagen I hydrogel microstructure by adjusting gelation temperature.
  • Incorporated Matrigel to modulate ECM composition and analyzed structural differences using microscopy.
  • Assessed vascular network formation, hCMEC growth, morphology, and maturity in response to varied ECM conditions.
  • Measured interleukin-8 (IL-8) secretion and evaluated angiogenic sprouting in preformed vascular networks.

Main Results:

  • Colder gelation temperatures increased collagen fiber thickness and length, with Matrigel further enhancing these structural changes.
  • Matrigel presence modulated hCMEC growth, while altered collagen microstructure affected vascular network morphology and maturity.
  • ECM-dependent changes in IL-8 secretion were observed.
  • Vascular networks formed in more fibrillar, Matrigel-containing hydrogels exhibited enhanced angiogenic sprouting.

Conclusions:

  • Both collagen hydrogel microstructure and ECM composition are critical, interacting factors that regulate vascular network formation.
  • These findings provide insights into the complex interplay between the ECM and endothelial cells, with implications for basic research and translational applications in regenerative medicine and disease modeling.