Tissue repair is often impaired in pathological states, highlighting the need for innovative wound-healing technologies. This study introduces composite hyaluronic acid gas-entrapping materials (GEMs) delivering carbon monoxide (CO) to promote wound healing in pigs. These composite materials facilitate burst release followed by sustained release of CO over 48 h. In a porcine full-thickness wound model, CO-GEMs significantly accelerated wound closure compared to the standard-of-care dressing (Tegaderm). Wound area closure with CO-GEMs was 68.6% vs 56.8% on day 14, 41.0% vs 25.1% on day 28, and 26.9% vs 11.8% on day 42, effectively reducing healing time by 14 days. Histological analysis revealed increased epithelialization and neovascularization with reduced inflammation. These findings demonstrate the potential of CO-GEMs as a topical therapeutic to enhance tissue repair in clinically relevant models, supporting further testing for wound-healing applications.