Synergistic CO2 Cryotherapy and EGF Delivery for Accelerated Wound Healing Through Anti-Inflammatory and Regenerative Pathways

Wound healing remains a significant clinical challenge worldwide, and effective management strategies are essential for improving outcomes. This study investigates the therapeutic potential of the AcuCool™ system, a novel multifunctional device that combines high-velocity CO₂ cryotherapy with intradermal delivery of epidermal growth factor (EGF), in promoting wound healing. Using a full-thickness skin wound model in Sprague Dawley rats, we compared the effects of Device+EGF treatment to those of conventional microneedling-based EGF delivery and untreated controls. Macroscopic assessments revealed significantly accelerated wound closure in the Device+EGF group. Histological analysis showed enhanced re-epithelialization, reduced inflammatory cell infiltration, and increased collagen deposition. Molecular evaluations further demonstrated downregulation of pro-inflammatory markers (TNF-α, IL-1β, MCP-1) and upregulation of remodeling-related genes including TGF-β1, Collagen I, and Vimentin. In addition, nitrite assays confirmed reduced local nitric oxide levels, indicating suppression of oxidative stress. The AcuCool™ platform offers precise, non-invasive drug delivery with dual physical and biochemical therapeutic mechanisms, enabling superior control of inflammation and tissue regeneration. These findings suggest that AcuCool™ represents a promising therapeutic strategy for accelerating wound healing in acute models. While further studies are warranted in chronic wound settings, this approach may hold translational potential for future clinical applications.