{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:14Z","timestamp":1760060654600,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Trade, Industry &amp; Energy (MOTIE, Republic of Korea)","award":["20022874"],"award-info":[{"award-number":["20022874"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2122 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-\u03b1, IL-1\u03b2, MCP-1) and upregulation of remodeling-related genes including TGF-\u03b21, Collagen I, and Vimentin. In addition, nitrite assays confirmed reduced local nitric oxide levels, indicating suppression of oxidative stress. The AcuCool\u2122 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\u2122 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.<\/jats:p>","DOI":"10.3390\/ijms26188796","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"8796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic CO2 Cryotherapy and EGF Delivery for Accelerated Wound Healing Through Anti-Inflammatory and Regenerative Pathways"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8672-7740","authenticated-orcid":false,"given":"Yongxun","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1447-2079","authenticated-orcid":false,"given":"Yong-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Ajou University, Suwon 16499, Republic of Korea"},{"name":"Korean Institute of Nonclinical Study (KINS), Seongnam 13605, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Do Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Korean Institute of Nonclinical Study (KINS), Seongnam 13605, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2982-943X","authenticated-orcid":false,"given":"Caijun","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-6341","authenticated-orcid":false,"given":"Xinrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Ryeong","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Ajou University, Suwon 16499, Republic of Korea"},{"name":"Research Institute of Pharmaceutical Sciences and Technology, Ajou University, Suwon 16499, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gun-Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"RecensMedical, Inc., Hwaseong-si 18468, Republic of Korea"},{"name":"Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"RecensMedical, Inc., Hwaseong-si 18468, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taek-In","family":"Oh","sequence":"additional","affiliation":[{"name":"Korean Institute of Nonclinical Study (KINS), Seongnam 13605, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7078-2077","authenticated-orcid":false,"given":"Yi-Sook","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Ajou University, Suwon 16499, Republic of Korea"},{"name":"Research Institute of Pharmaceutical Sciences and Technology, Ajou University, Suwon 16499, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pham Ngoc","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-7365","authenticated-orcid":false,"given":"Chan Yeong","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"},{"name":"Korean Institute of Nonclinical Study (KINS), Seongnam 13605, Republic of Korea"},{"name":"Department of Medical Device Development, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","first-page":"3706315","article-title":"Skin Acute Wound Healing: A Comprehensive Review","volume":"2019","year":"2019","journal-title":"Int. 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