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Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...

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Accelerating vascularization in polycaprolactone scaffolds by endothelial progenitor cells.

Shivani Singh1, Benjamin M Wu, James C Y Dunn

  • 1Department of Bioengineering, University of California, Los Angeles, California 90095, USA.

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|March 15, 2011
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This study enhances blood vessel formation in porous polycaprolactone (PCL) scaffolds using endothelial progenitor cells (EPCs) and vascular endothelial growth factor (VEGF). Heparin-immobilized scaffolds with EPCs and VEGF significantly accelerated vascularization and host integration.

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Vascular Biology

Background:

  • Vascularization is critical for the success of tissue engineering scaffolds.
  • Polycaprolactone (PCL) scaffolds lack inherent vascularization properties.
  • Endothelial progenitor cells (EPCs) hold promise for promoting angiogenesis.

Purpose of the Study:

  • To accelerate blood vessel formation within porous PCL scaffolds.
  • To investigate the role of surface-immobilized heparin and vascular endothelial growth factor (VEGF) in enhancing EPC function.
  • To optimize EPC density for uniform vascularization in engineered tissues.

Main Methods:

  • EPCs were seeded onto PCL scaffolds with surface-immobilized heparin and VEGF.
  • Scaffolds were implanted subcutaneously in immunodeficient mice for 7 days.
  • Vessel density, anastomosis with host circulation, and EPC apoptosis were analyzed.
  • The effect of EPC density and in vitro expansion on vasculogenic potential was assessed.

Main Results:

  • Heparin-immobilized PCL scaffolds with VEGF significantly increased blood vessel density.
  • Anastomosis between EPC-derived vessels and host circulation was confirmed by murine erythrocyte presence.
  • Optimal EPC density promoted uniform vascularization, while excessive density led to apoptosis and reduced inner-core vascularization.
  • Co-seeding with other cells and limited in vitro expansion maintained EPC vasculogenic potential.

Conclusions:

  • Surface-immobilized heparin and VEGF effectively promote EPC-driven vascularization in PCL scaffolds.
  • Controlling EPC density is crucial for achieving uniform vascularization and preventing apoptosis within engineered tissues.
  • EPCs retain their ability to accelerate vascularization in composite cell constructs and when not excessively expanded in vitro.