Nanobubble-Mediated Oxygen Delivery Mitigates Hypoxia-Induced ROS and HIF-1α Expression in UC-MSCs

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cell Biology

Background:

• Hypoxia and nutrient deprivation challenge transplanted cell survival.
• Controllable oxygen delivery is crucial for stem cell therapies.
• Human umbilical cord mesenchymal stem cells (UC-MSCs) are vulnerable to harsh microenvironments.

Purpose of the Study:

• To engineer oxygen nanobubbles (TONBs) for enhanced UC-MSC survival.
• To evaluate the cytoprotective effects of TONBs in a 2D ischemia-mimetic model.
• To assess TONBs' capacity for oxygen buffering and mitigation of hypoxia-induced stress.

Main Methods:

• Fluorosurfactant-coated oxygen nanobubbles (TONBs) were engineered and characterized (nanoparticle tracking analysis, zeta potential).
• Dissolved oxygen (DO) release from TONBs was quantified in DMEM.
• UC-MSCs were subjected to hypoxic stress (1% O2) with and without TONB treatment.
• Cellular metabolic activity, viability, mitochondrial ROS, and HIF-1α expression were assessed.

Main Results:

• TONBs exhibited stable sub-200 nm size and high colloidal stability (-58 mV).
• TONBs significantly increased dissolved oxygen levels in culture media (~18 ppm vs. ~8 ppm).
• TONB treatment preserved metabolic activity and viability, reduced ROS by ~20%, and downregulated HIF-1α (~8-9 fold) under hypoxia.

Conclusions:

• TONBs effectively buffer oxygen, mitigating hypoxia-driven metabolic stress in UC-MSCs.
• TONBs demonstrate potential as an oxygen delivery adjunct for regenerative medicine.
• This technology supports enhanced cell survival and function in engineered tissues.