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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...
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Programming Stem Cells for Therapeutic Angiogenesis Using Biodegradable Polymeric Nanoparticles
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Hierarchically Structured Biodegradable Microspheres Promote Therapeutic Angiogenesis.

Eseelle K Hendow1, Francesco Iacoviello2, Mar Casajuana Ester1

  • 1Centre for Precision Healthcare, UCL Division of Medicine, University College London, Gower Street, London, WC1E 6BT, UK.

Advanced Healthcare Materials
|September 11, 2024
PubMed
Summary
This summary is machine-generated.

Biodegradable porous microspheres enhance blood flow and vessel density in ischemic tissue. This novel approach harnesses macrophage responses for therapeutic neovascularization, offering a promising alternative to biological therapies.

Keywords:
macrophagesmicrospheresneovascularizationtherapeutic angiogenesisthermally induced phase separation

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • Neovascularization is crucial for tissue engineering and cardiovascular disease treatment.
  • Acellular materials offer advantages over biological therapies but face immune response challenges.
  • Macrophages, key immune cells, can be leveraged to stimulate blood vessel growth.

Purpose of the Study:

  • To investigate the efficacy of biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres in promoting neovascularization.
  • To evaluate the impact of microsphere structure (porous vs. solid) on tissue perfusion.
  • To explore the underlying immunological mechanisms, particularly macrophage polarization and growth factor secretion.

Main Methods:

  • Utilized biodegradable PLGA microspheres with hierarchical porous structures.
  • Implanted microspheres in a hind limb ischemia model in rodents.
  • Assessed blood flow and blood vessel density post-implantation.
  • Simulated foreign body response in vitro, analyzing macrophage (M1/M2) interactions and vascular endothelial growth factor (VEGF) secretion.

Main Results:

  • Porous PLGA microspheres significantly increased blood flow and blood vessel density by day 21 compared to solid microspheres.
  • In vitro studies showed M2-like macrophages incubated with porous microspheres secreted higher levels of VEGF than M1-like macrophages.
  • This suggests a mechanism where porous microspheres modulate macrophage response to promote angiogenesis.

Conclusions:

  • Implantable biodegradable porous microspheres represent a novel strategy for enhancing neovascularization.
  • This approach effectively restores tissue perfusion in ischemic conditions.
  • The findings support the therapeutic potential of engineered microspheres for cardiovascular applications and tissue regeneration.