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Acute Three-Dimensional Hypoxia Regulates Angiogenesis.

Publication ,  Journal Article
Ntekoumes, D; Song, J; Liu, H; Amelung, C; Guan, Y; Gerecht, S
Published in: Advanced healthcare materials
January 2025

Hypoxia elicits a multitude of tissue responses depending on the severity and duration of the exposure. While chronic hypoxia is shown to impact development, regeneration, and cancer, the understanding of the threats of acute (i.e., short-term) hypoxia is limited mainly due to its transient nature. Here, a novel gelatin-dextran (Gel-Dex) hydrogel is established that decouples hydrogel formation and oxygen consumption and thus facilitates 3D sprouting from endothelial spheroids and, subsequently, induces hypoxia "on-demand." The Gel-Dex platform rapidly achieves acute moderate hypoxic conditions without compromising its mechanical properties. Acute exposure to hypoxia leads to increased endothelial cell migration and proliferation, promoting the total length and number of vascular sprouts. This work finds that the enhanced angiogenic response is mediated by reactive oxygen species, independently of hypoxia-inducible factors. Reactive oxygen species-dependent matrix metalloproteinases activity mediated angiogenic sprouting is observed following acute hypoxia. Overall, the Gel-Dex hydrogel offers a novel platform to study how "on-demand" acute moderate hypoxia impacts angiogenesis, with broad applicability to the development of novel sensing technologies.

Duke Scholars

Published In

Advanced healthcare materials

DOI

EISSN

2192-2659

ISSN

2192-2640

Publication Date

January 2025

Volume

14

Issue

2

Start / End Page

e2403860

Related Subject Headings

  • Spheroids, Cellular
  • Reactive Oxygen Species
  • Neovascularization, Physiologic
  • Hypoxia
  • Hydrogels
  • Humans
  • Human Umbilical Vein Endothelial Cells
  • Gelatin
  • Dextrans
  • Cell Proliferation
 

Citation

APA
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ICMJE
MLA
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Ntekoumes, D., Song, J., Liu, H., Amelung, C., Guan, Y., & Gerecht, S. (2025). Acute Three-Dimensional Hypoxia Regulates Angiogenesis. Advanced Healthcare Materials, 14(2), e2403860. https://doi.org/10.1002/adhm.202403860
Journal cover image

Published In

Advanced healthcare materials

DOI

EISSN

2192-2659

ISSN

2192-2640

Publication Date

January 2025

Volume

14

Issue

2

Start / End Page

e2403860

Related Subject Headings

  • Spheroids, Cellular
  • Reactive Oxygen Species
  • Neovascularization, Physiologic
  • Hypoxia
  • Hydrogels
  • Humans
  • Human Umbilical Vein Endothelial Cells
  • Gelatin
  • Dextrans
  • Cell Proliferation