{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:07:23Z","timestamp":1768565243200,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Lasers Surg Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>One symptom of hypertrophic scar (HTS) that can develop after burn injury is dyschromia with hyper\u2010 and hypopigmentation. There are limited treatments for these conditions. Previously, we showed there is no expression of alpha melanocyte stimulating hormone (\u03b1\u2010MSH) in hypopigmented scars, and if these melanocytes are treated with synthetic \u03b1\u2010MSH in vitro, they respond by repigmenting. The current study tested the same hypothesis in the in vivo environment using laser\u2010assisted drug delivery (LADD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HTSs were created in red Duroc pigs. At Day 77 (pre), they were treated with CO<jats:sub>2<\/jats:sub> fractional ablative laser (FLSR). Synthetic \u03b1\u2010MSH was delivered as a topical solution dissolved in\u00a0\n<jats:sc>l<\/jats:sc>\u2010tyrosine (<jats:italic>n<\/jats:italic>\u2009=\u20096, treated). Control scars received LADD of\u00a0\n<jats:sc>l<\/jats:sc>\u2010tyrosine only (<jats:italic>n<\/jats:italic>\u2009=\u20092, control). Scars were treated and examined weekly through Week 4. Digital images and punch biopsies of hyper, hypo\u2010, and normally pigmented scar and skin were collected. Digital pictures were analyzed with ImageJ by tracing the area of hyperpigmentation. Epidermal sheets were obtained from punch biopsies through dispase separation and RNA was isolated. qRT\u2010PCR was run for melanogenesis\u2010related genes: tyrosinase (TYR), tyrosinase\u2010related protein\u20101 (TYRP1), and dopachrome tautomerase (DCT). Two\u2010way ANOVA with multiple comparisons and Dunnett's correction compared the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The areas of hyperpigmentation were variable before treatment. Therefore, data is represented as fold\u2010change where each scar was normalized to its own pre value. Within the LADD of NDP \u03b1\u2010MSH\u2009+\u2009<jats:sc>l<\/jats:sc>\u2010tyrosine group, hyperpigmented areas gradually increased each week, reaching 1.3\u2010fold over pre by Week 4. At each timepoint, area of hyperpigmentation was greater in the treated versus the control (1.04\u2009\u00b1\u20090.05 vs. 0.89\u2009\u00b1\u20090.08, 1.21\u2009\u00b1\u20090.07 vs. 0.98\u2009\u00b1\u20090.24, 1.21\u2009\u00b1\u20090.08 vs. 1.04\u2009\u00b1\u20090.11, 1.28\u2009\u00b1\u20090.11 vs. 0.94\u2009\u00b1\u20090.25; fold\u2010change from pre\u2010). Within the treatment group, pretreatment, levels of TYR were decreased \u221217.76\u2009\u00b1\u20094.52 below the level of normal skin in hypopigmented scars. After 1 treatment, potentially due to laser fractionation, the levels decreased to \u221243.49\u2009\u00b1\u20095.52. After 2, 3, and 4 treatments, there was ever increasing levels of TYR to almost the level of normally pigmented skin (\u221235.74\u2009\u00b1\u200915.72, \u221223.25\u2009\u00b1\u20096.80, \u22125.52\u2009\u00b1\u20092.22 [<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, Week 4]). This pattern was also observed for TYRP1 (pre\u2009=\u2009\u221212.94\u2009\u00b1\u20091.82, Week 1\u2009=\u2009\u221248.85\u2009\u00b1\u200913.25 [<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01], Weeks 2, 3, and 4\u2009=\u2009\u221234.45\u2009\u00b1\u200914.64, \u221228.19\u2009\u00b1\u20094.98, \u22126.93\u2009\u00b1\u20093.05 [<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, Week 4]) and DCT (pre\u2009=\u2009\u2212214.95\u2009\u00b1\u200989.42, Week 1\u2009=\u2009\u2212487.93\u2009\u00b1\u2009126.32 [<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05], Weeks 2, 3, and 4\u2009=\u2009\u2212219.06\u2009\u00b1\u200979.33, \u221272.91\u2009\u00b1\u200920.45 [<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001], \u221276.00\u2009\u00b1\u200924.26 [<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001]). Similar patterns were observed for scars treated with LADD of\u00a0\n<jats:sc>l<\/jats:sc>\u2010tyrosine alone without NDP \u03b1\u2010MSH. For each gene, in hyperpigmented scar, levels increased at Week 4 of treatment compared to Week 1 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A clinically\u2010relevant FLSR treatment method can be combined with topical delivery of synthetic \u03b1\u2010MSH and\u00a0<jats:sc>l<\/jats:sc>\u2010tyrosine to increase the area of pigmentation and expression of melanogenesis genes in hypopigmented HTS. LADD of\u00a0\n<jats:sc>l<\/jats:sc>\u2010tyrosine alone leads to increased expression of melanogenesis genes. Future studies will aim to optimize drug delivery, timing, and dosing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/lsm.23663","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T08:30:06Z","timestamp":1681374606000},"page":"490-502","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Laser\u2010assisted drug delivery of synthetic alpha melanocyte stimulating hormone and L\u2010tyrosine leads to increased pigmentation area and expression of melanogenesis genes in a porcine hypertrophic scar model"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2292-4960","authenticated-orcid":false,"given":"Bonnie C.","family":"Carney","sequence":"first","affiliation":[{"name":"Firefighters' Burn and Surgical Research Laboratory MedStar Health Research Institute Washington District of Columbia USA"},{"name":"Department of Surgery Georgetown University School of Medicine 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USA"},{"name":"Department of Surgery Georgetown University School of Medicine  Washington District of Columbia USA"},{"name":"Department of Biochemistry and Molecular &amp; Cellular Biology Georgetown University Medical Center  Washington District of Columbia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey W.","family":"Shupp","sequence":"additional","affiliation":[{"name":"Firefighters' Burn and Surgical Research Laboratory MedStar Health Research Institute Washington District of Columbia USA"},{"name":"Department of Surgery Georgetown University School of Medicine  Washington District of Columbia USA"},{"name":"Department of Biochemistry and Molecular &amp; Cellular Biology Georgetown University Medical Center  Washington District of Columbia USA"},{"name":"Department of Surgery, The Burn Center MedStar Washington Hospital Center Washington District of Columbia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taryn E.","family":"Travis","sequence":"additional","affiliation":[{"name":"Firefighters' Burn and Surgical Research Laboratory MedStar Health Research Institute Washington District of Columbia USA"},{"name":"Department of Surgery Georgetown University School of Medicine  Washington District of Columbia USA"},{"name":"Georgetown University School of Medicine Washington District of Columbia 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