Wound healing involves multiple interrelated processes required to lead to successful healing outcomes. Phagocytosis, inflammation, cell proliferation, angiogenesis, energy production, and collagen synthesis are all directly or indirectly dependent on oxygen. Along with other critical factors, such as nutrition and comorbidities, availability of oxygen is a key determinant of healing success. Previously, we have presented a novel oxygenated hydrogel material that can be made into dressings for continuous localized oxygen delivery to wounds. In this study, an acute porcine wound model was used to test the healing benefits of these oxygenated MACF (MACF + O2) hydrogel dressings compared to controls, which included commercial Derma-GelTM hydrogel dressings. Wound closure and histological analyses were performed to assess re-epithelialization, collagen synthesis, angiogenesis, and keratinocyte maturation. Results from these assays revealed that wounds treated with MACF + O2 hydrogel dressings closed faster as compared to Derma-Gel (p<0.05). Targeted metabolomics via liquid chromatography separation and mass spectrometric detection (LC-MS/MS) and a biochemical assay determined the concentration of hydroxyproline in wound samples at days 14 and 21, showing that MACF + O2 hydrogel dressings improved wound healing via an upregulated collagen synthesis pathway as compared to Derma-Gel (p<0.05). Histological evidence showed that MACF + O2 hydrogel dressings improve new blood vessel formation and keratinocyte maturation over all other treatments.