Oxygen-generating microparticles downregulate HIF-1α expression, increase cardiac contractility, and mitigate...

Area of Science:

• Biomaterials Science
• Cardiovascular Research
• Regenerative Medicine

Background:

• Myocardial hypoxia, or low oxygen in heart tissue, is a critical factor in cardiac diseases and post-transplant complications.
• Oxygen-generating microparticles offer a promising therapeutic strategy to sustain cardiac cell and tissue viability under hypoxic conditions.

Purpose of the Study:

• To develop and evaluate biodegradable oxygen-generating microparticles for sustained oxygen release.
• To investigate the impact of these microparticles on cardiomyocyte metabolic activity, viability, and gene expression during hypoxia.
• To assess the functional recovery of cardiac tissue mechanics and reduce myocardial injury in ex vivo models.

Main Methods:

• Fabrication of poly D,L-lactic-co-glycolic acid and calcium peroxide (CPO) microparticles for sustained oxygen release (up to 24 hours).
• Assessment of primary rat cardiomyocyte metabolic activity and viability under hypoxia.
• Measurement of hypoxia-inducible factor (HIF)-1α expression levels.
• Single-cell traction force microscopy to evaluate cellular energy generation and tissue contractility.
• Evaluation of engineered cardiac tissues and ex vivo rabbit hearts treated with CPO microparticles.

Main Results:

• CPO microparticles demonstrated sustained oxygen release and increased cardiomyocyte metabolic activity without compromising cell viability during hypoxia.
• Oxygen delivery via CPO microparticles effectively downregulated hypoxia-inducible factor (HIF)-1α.
• Restoration of cellular energy generation and enhanced contractility were observed in hypoxic cells and engineered cardiac tissues treated with CPO microparticles.
• Significant reduction in myocardial injury was observed in ex vivo rabbit hearts treated with CPO microparticles compared to controls.

Conclusions:

• Biodegradable CPO microparticles provide sustained oxygen release, improving cardiac cell and tissue function under hypoxic conditions.
• These microparticles mitigate hypoxia-induced myocardial injuries, showing potential for applications in organ transplantation and cardiac tissue engineering.
• The study highlights the efficacy of oxygen-releasing microparticles in restoring cardiac mechanics and reducing injury, addressing critical needs in cardiovascular medicine.