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Updated: Nov 1, 2025
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Quantitative and Temporal Control of Oxygen Microenvironment at the Single Islet Level
Published on: November 17, 2013
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Discretizing Three-Dimensional Oxygen Gradients to Modulate and Investigate Cellular Processes
Michael R Blatchley1,2, Franklyn Hall1,2, Dimitris Ntekoumes2
1Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|June 21, 2021
Summary
Engineered hydrogels precisely control oxygen levels, revealing novel regulators of blood vessel formation under hypoxia. This platform aids study of cellular responses in 3D hypoxic environments for development and disease.
Area of Science:
- Biomedical Engineering
- Cellular Biology
- Biomaterials Science
Background:
- Cellular processes are significantly affected by oxygen deprivation (hypoxia).
- Engineered systems are being developed to control oxygen concentrations and create biomimetic oxygen gradients for studying cellular behavior.
- Existing 3D platforms with oxygen gradients lead to diverse cell behaviors, complicating the study of oxygen-sensitive signaling pathways.
Purpose of the Study:
- To develop a layer-by-layer assembled, oxygen-controllable hydrogel system for precise oxygen concentration control.
- To study uniform cell behavior in discretized oxygen gradients and recapitulate cluster-based vasculogenesis.
- To identify novel regulators of hypoxic cluster-based vasculogenesis and assess the platform's utility for studying dynamic cellular responses in 3D hypoxic environments.
Main Methods:
- Utilized a layer-by-layer assembled oxygen-controllable hydrogel.
- Recapitulated cluster-based vasculogenesis dynamics.
- Employed RNA sequencing to analyze gene expression patterns and identify signaling pathways.
- Investigated the role of extracellular matrix modulators and cell-cell interaction regulators.
Main Results:
- Distinctive gene expression patterns were observed that correlated with oxygen concentrations.
- Time-dependent regulation of cyclic adenosine monophosphate signaling was found to enable cell survival and clustering in high-stress microenvironments.
- Extracellular matrix modulators and regulators of cell-cell interactions, notably vascular cell adhesion molecule 1, were identified as key facilitators of hypoxia-driven endothelial cell clustering.
Conclusions:
- Novel regulators of hypoxic cluster-based vasculogenesis have been identified.
- The developed hydrogel platform offers a unique tool for studying dynamic cellular responses to 3D hypoxic environments.
- The findings have broad applicability in the fields of development, regeneration, and disease research.
