Jin Yongxun, Lee Yong-Hyun, Kim Do Hwan, Jin Caijun, Zhang Xinrui, Yoo Jae Ryeong, Kim Gun-Ho, Kim Dae Hyun, Oh Taek-In, Jung Yi-Sook, Chien Pham Ngoc, Heo Chan Yeong
Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea.
Int J Mol Sci. 2025 Sep 10;26(18):8796. doi: 10.3390/ijms26188796.
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 CO 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.
伤口愈合在全球范围内仍然是一项重大的临床挑战，有效的管理策略对于改善治疗效果至关重要。本研究调查了AcuCool™系统的治疗潜力，该系统是一种新型多功能设备，将高速CO2冷冻疗法与表皮生长因子（EGF）的皮内递送相结合，以促进伤口愈合。我们使用Sprague Dawley大鼠的全层皮肤伤口模型，比较了设备+EGF治疗与传统微针介导的EGF递送及未治疗对照组的效果。宏观评估显示，设备+EGF组的伤口闭合明显加速。组织学分析表明，上皮再形成增强，炎症细胞浸润减少，胶原蛋白沉积增加。分子评估进一步表明，促炎标志物（TNF-α、IL-1β、MCP-1）下调，包括TGF-β1、胶原蛋白I和波形蛋白在内的重塑相关基因上调。此外，亚硝酸盐检测证实局部一氧化氮水平降低，表明氧化应激受到抑制。AcuCool™平台提供精确的非侵入性药物递送，具有双重物理和生化治疗机制，能够更好地控制炎症和组织再生。这些发现表明，AcuCool™代表了一种在急性模型中加速伤口愈合的有前景的治疗策略。虽然在慢性伤口环境中还需要进一步研究，但这种方法可能具有未来临床应用的转化潜力。
