{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:43:20Z","timestamp":1773297800106,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["P41EB015890"],"award-info":[{"award-number":["P41EB015890"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Lasers Surg Med"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Injury to healthy dermis and the dermoepidermal junction initiates a robust healing process consisting of fibrous tissue overgrowth, collagen deposition, and scar formation. The conventional management of scars and other skin injuries has largely relied upon surgical soft tissue transfer to resurface and\/or replace damaged and dysmorphic tissue with new skin. However, these strategies are invasive, expensive, and may further exacerbate integumentary injury. In this study, we examine the creation of <jats:italic>in situ<\/jats:italic> redox generated pH changes in fresh human skin. We believe this process of \u201celectrochemical therapy\u201d (ECT) leads to changes in collagen matrix structure. Our objective is to map local tissue pH landscapes and image changes in collagen structure of non\u2010injured skin following ECT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p><jats:italic>Ex vivo<\/jats:italic> human study involving ECT of human skin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Remnant fresh <jats:italic>ex vivo<\/jats:italic> human facial skin from facelift operations was enveloped in saline\u2010soaked gauze for a maximum of 2 hours prior to ECT and imaging. ECT was performed by inserting platinum\u2010plated needle electrodes connected to a DC power supply. Voltage (4, 5, or 6\u2009V) and time (3, 4, or 5\u2009minutes) were varied systematically. High frequency ultrasound (25\u2009MHz) was performed immediately after ECT on each sample. Treated samples were also imaged using multiphoton microscopy (MPM) with second harmonic generation (SHG) to specifically visualize collagen fibers in the dermis. The pH landscapes were mapped using indicator dyes in bisected specimens and the MPM images were compared with histologic findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Above 4\u2009V and 3\u2009minutes, a profound reduction in dermal collagen SHG signal was observed at the anode. Although there was less blunting of SHG signal seen at the cathode, a decrease in the fluorescence of the dermoepidermal junction was observed. The pH application suggests ECT spatial selectivity and a direct relationship between voltage and application time. Ultrasound demonstrated gas formation between the anode and cathode, which is consistent with ECT's mechanism of action. Importantly, these electrochemical changes occurred without disrupting dermal and epidermal histologic architecture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ECT alters tissue pH leading to dermal collagen structural change. These results offer additional insight into the translational potential of ECT to locally remodel the soft\u2010tissue matrix. Future directions aim to expand into a skin injury model to determine if similar collagen effects are observed <jats:italic>in vivo<\/jats:italic>. ECT is incredibly inexpensive (~$5) and may be a means to treat soft tissue injuries using simple needle\u2010based devices and DC battery power supplies. Lasers Surg. Med. \u00a9 2019 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/lsm.23094","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T07:20:58Z","timestamp":1558682458000},"page":"196-206","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Multiphoton Microscopy of Collagen Structure in Ex Vivo Human Skin Following Electrochemical Therap<b>y<\/b>"],"prefix":"10.1002","volume":"52","author":[{"given":"Allison C.","family":"Hu","sequence":"first","affiliation":[{"name":"School of Medicine University of California Irvine California 92617"},{"name":"Beckman Laser Institute and Medical Clinic University of California Irvine California 92612"},{"name":"Department of Biomedical Engineering University of California Irvine California 92617"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen M.","family":"Hong","sequence":"additional","affiliation":[{"name":"Beckman Laser Institute and Medical Clinic University of California Irvine California 92612"},{"name":"Department of Biomedical Engineering University of California Irvine California 92617"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Toubat","sequence":"additional","affiliation":[{"name":"Keck School of Medicine of USC Los Angeles California 90033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Sivoraphonh","sequence":"additional","affiliation":[{"name":"Beckman Laser Institute and Medical Clinic University of California Irvine California 92612"},{"name":"Department of Biomedical Engineering University of California Irvine California 92617"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Barnes","sequence":"additional","affiliation":[{"name":"Beckman Laser Institute and Medical Clinic University of California Irvine California 92612"},{"name":"Department of Biomedical Engineering University of California Irvine California 92617"},{"name":"Department of Otolaryngology\u2013Head and Neck Surgery University of California Irvine, Orange California 92868"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wesley J.","family":"Moy","sequence":"additional","affiliation":[{"name":"Beckman Laser Institute and Medical Clinic University of California Irvine California 92612"},{"name":"Department of Biomedical Engineering University of California Irvine California 92617"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana B.","family":"Krasieva","sequence":"additional","affiliation":[{"name":"Beckman Laser Institute and Medical Clinic University of California Irvine California 92612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian J. 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