Oxygen Nanobubbles-Embedded Hydrogel as Wound Dressing to Accelerate Healing

Abstract

Herein, we propose an oxygen nanobubbles-embedded hydrogel (ONB-G) with carbopol for oxygenation of wounds to accelerate the wound healing process. We integrate carbopol, hydrogel, and dextran-based oxygen nanobubbles (ONBs) to prepare ONB-G where ONBs can hold and release oxygen to accelerate wound healing. Oxygen release tests showed that the proposed ONB-G could encapsulate oxygen in the hydrogels for up to 34 days; meanwhile, fluorescence studies indicated that the ONB-G could maintain high oxygen levels for up to 4 weeks. The effect of carbopol concentration on the oxygen release capacity and rheological features of the ONB-G were also investigated along with the sterility of ONB-G. HDFa cell-based studies were first conducted to evaluate the viability, proliferation, and revival of cells in hypoxia. Scratch assay and mRNA expression studies indicated the potential benefit for wound closure. Histological evaluation of tissues with a pig model with incision and punch wounds showed that treatment with ONB-G exhibited improved healing compared with hydrogel without ONBs or treated without the gel. Our studies show that dextran-shell ONBs embedded in a gel (ONB-G) have the potential to accelerate wound healing, given its oxygen-holding capacity and release properties.

Hydrogel-Based Oxygen and Drug Delivery Dressing for Improved Wound Healing

“…It can be seen that there is no significant change in oxygen released over a 3-week storage period at 4 °C. A slight increase in the oxygen release over the storage period was noted, which is similar to that observed in the ONB-embedded Carbopol hydrogel that was proposed in our prior work . This increase could be attributed to the aging process of the Carbopol-based hydrogel .…”

“…Under hypoxic conditions, oxygen supply would aid in cell migration for an accelerated wound closure, which was presented with a fast closure in a cell scratch assay. , Meanwhile, in the proposed ONB-CC, the loaded collagenase would also improve cell migration for better wound closure . Thus, it could be expected that the ONB-CC would exhibit an enhanced capacity to improve wound healing.…”

“…For the first strategy, hydrogels were made with dissolved oxygen or oxygen-embedded nanostructures. 17 , 18 Dissolved oxygen could provide only a limited amount of oxygen, while the stored oxygen would be lost in a short period. However, with oxygen-embedded nanostructures, such as dextran-based oxygen nanobubbles (ONBs), the hydrogel could carry more oxygen, while the oxygen stored in the ONBs would be more stable in the hydrogel for a significantly increased storage time.…”

“…However, with oxygen-embedded nanostructures, such as dextran-based oxygen nanobubbles (ONBs), the hydrogel could carry more oxygen, while the oxygen stored in the ONBs would be more stable in the hydrogel for a significantly increased storage time. 18 , 19 For the second strategy, catalysts or enzymes that could accelerate oxygen-generating reactions were loaded in the hydrogels, and substrates such as H 2 O 2 were added to generate oxygen when the hydrogels were applied to wounds. 15 , 20 − 22 Meanwhile, bioactive species could also be loaded into hydrogels to generate oxygen to improve wound healing.…”

Exosome-coated oxygen nanobubble-laden hydrogel augments intracellular delivery of exosomes for enhanced wound healing

“…To demonstrate the injectability of the hydrogel, the stained hydrogel was loaded into a syringe with an inner diameter of 4.7 mm and subsequently extruded to form the shape of “UIUC”. Oxygen release within 48 h was monitored by Orion™ Versa Star Pro™ Dissolved Oxygen Electrochemistry Benchtop Meter (ThermoFisher Scientific) using a previously developed methodology 60 .…”