## Materials and Methods  
### Preparation of the ORHS  
To use the developed dressing as an effective remedy for skin defects, H\({}_{2}\)O\({}_{2}\) was dispersed intoPLGA microspheres in a 3D hydrogel sponge to control the oxygen concentration and cover the wound surface to prevent primary infection (Figure 1).  
H\({}_{2}\)O\({}_{2}\) in the PLGA microsphere was produced using the solvent evaporation method (W\({}_{1}\)/O/W\({}_{2}\)) [20]. Briefly, 200 mg of poly(lactic-co-glycolic acid) (PLGA, lactic acid/glycolic acid (LA:GA, 50:50, MW = 11,000 g/mol, Boehringer Ingelheim, Ingelheim am Rhein, Germany) was dissolved in 1.5 mL of dichloromethane (DCM, Junsei Chemical, Tokyo, Japan) (represented as O). Then, 750 mL of 4.0 wt% hydrogen peroxide (H\({}_{2}\)O\({}_{2}\), 50 wt%, Sigma, St. Louis, MO, USA) (represented as W\({}_{1}\)) was added to the mixture, which was then turned into an emulsion by high-speed stirring [W\({}_{1}\)/O]. Then, the [W\({}_{1}\)/O] emulsion was slowly poured into 4 mL of 3.5 wt% polyvinyl alcohol solution (PVA, MW = 9000-11,000 g/mol, Sigma, St. Louis, MO, USA) (represented as W\({}_{2}\)), followed by 30 s of high-speed stirring. Then, the [W\({}_{1}\)/O/W\({}_{2}\)] emulsion was slowly poured into 40 mL of 3.5 wt% PVA, the speed was adjusted to 800 rpm and the reaction was left at room temperature for 4 h. When the reaction was complete, the H\({}_{2}\)O\({}_{2}\)-PLGA microspheres (oxygen-release microspheres; ORM) were filtered through a 50-250 \(\upmu\)m sieve and rinsed thrice with distilled water to completely remove  
Figure 1: Concept of wound healing using H\({}_{2}\)O\({}_{2}\)-poly(lactic-co-glycolic acid) (PLGA) microspheres (oxygen-releasing microspheres, ORM) embedded oxygen-releasing hydrogel sponge(ORHS): PLGA poly(lactic-co-glycolic acid), PLL(poly-t-lysine hydrobromide).  
any unreacted species. The clean ORM was dried at room temperature for 18 h and stored at \(-20\)\({}^{\circ}\)C for subsequent use (Figure 2A).  
The ORHS was prepared using the freeze-drying method [21]. Briefly, 20 mg of ORM was added to 20 mL of 1.0 wt% sodium alginate (LVG, viscosity: 20-200 mPa-s, NovaMatrix, Sandvika, Norway) and uniformly mixed. Following this, 500 uL aliquots were distributed into each well (well size: 85.4 \(\times\) 127.6 mm, height 9.75 mm), and the plate was placed inside a lyophilizer (Ilshin Lab, FD5505, Gyeonggi-do, Korea) for 48 h for freeze-0000 drying. Next, 1.0 wt% calcium chloride dehydrate (CaCl\({}_{2}\).2H\({}_{2}\)O, Sigma, St. Louis, MO, USA) was added to each well, and the plate was left at room temperature for 24 h to allow for cross-linking to occur, after which the plate was then rinsed five times with distilled water and 95% ethyl alcohol to completely remove the calcium solution. The plate was again placed inside a lyophilized for 48 h for freeze-drying, followed by coating through a 5 min immersion in 0.1 wt% poly-L-lysine hydrobromide (PLL, Sigma, St. Louis, MO, USA). After rinsing three times with distilled water, and complete drying inside the lyophilized, the ORHS plate was stored at\(-20\)\({}^{\circ}\)C until subsequent use (Figure 2B).  
All chemicals and solvents used in the study were of analytical reagent grade.  
Figure 2: (**A**) Encapsulation process of H\({}_{2}\)O\({}_{2}\)-PLGA microspheres (oxygen-releasing microspheres, ORM) using the double emulsion solvent evaporation method, (**B**) Schematic diagram showing the fabrication process of the ORHS (oxygen-releasing hydrogel sponge): poly(lactic-co-glycolic acid), PLL(poly-L-lysine hydrobromide), PVA(polyvinyl alcohol).