{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:21:50Z","timestamp":1793748110023,"version":"4.6.1"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["BOE 22\/10\/2019"],"award-info":[{"award-number":["BOE 22\/10\/2019"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/02083"],"award-info":[{"award-number":["PI17\/02083"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Regional Government of Andalusia","award":["PIGE-0242-2019"],"award-info":[{"award-number":["PIGE-0242-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In recent years, new therapies, such as skin cell lines injections, have emerged to promote re-epithelialization of damaged areas such as chronic ulcers or to treat patients with severe burns. Antiseptics are commonly used during wound clinical management to avoid serious infections, but they may delay the healing process due to their apparent cytotoxicity to skin cells. The cytotoxicity of ethanol, chlorhexidine digluconate, sodium hypochlorite, povidone iodine and polyhexanide was evaluated in this in vitro study on human fibroblasts and keratinocytes. Treatments were applied to each cell type culture every 48 h for 14 days. To determine the cytotoxic of antiseptics, cell viability (Live\/Dead\u00ae) and cell proliferation (AlamarBlue\u2122) assays were performed on cell monolayers. Cell migration capacity was evaluated with a wound closure assay. Results showed how chlorhexidine digluconate and ethanol significantly reduced the viability of keratinocytes and inhibited cell migration. Povidone iodine followed by chlorhexidine digluconate significantly reduced fibroblast cell viability. Povidone iodine also inhibited cell migration. Sodium hypochlorite was the least detrimental to both cell types. If epithelial integrity is affected, the wound healing process may be altered, so the information gathered in this study may be useful in selecting the least aggressive antiseptic after treatment with new emerging therapies.<\/jats:p>","DOI":"10.3390\/cells11091395","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T01:55:51Z","timestamp":1650506151000},"page":"1395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Cytotoxicity and Wound Closure Evaluation in Skin Cell Lines after Treatment with Common Antiseptics for Clinical Use"],"prefix":"10.3390","volume":"11","author":[{"given":"Laura","family":"Ortega-Llamas","sequence":"first","affiliation":[{"name":"Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain"},{"name":"Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain"},{"name":"Andalusian Network of Design and Translation of Advanced Therapies, 41092 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4984-1017","authenticated-orcid":false,"given":"Mar\u00eda I.","family":"Qui\u00f1ones-Vico","sequence":"additional","affiliation":[{"name":"Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain"},{"name":"Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain"},{"name":"Andalusian Network of Design and Translation of Advanced Therapies, 41092 Seville, Spain"},{"name":"Dermatology Department, School of Medicine, University of Granada, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Garc\u00eda-Valdivia","sequence":"additional","affiliation":[{"name":"Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain"},{"name":"Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain"},{"name":"Andalusian Network of Design and Translation of Advanced Therapies, 41092 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6852-0836","authenticated-orcid":false,"given":"Ana","family":"Fern\u00e1ndez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain"},{"name":"Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain"},{"name":"Andalusian Network of Design and Translation of Advanced Therapies, 41092 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1311-8035","authenticated-orcid":false,"given":"Ana","family":"Ubago-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain"},{"name":"Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain"},{"name":"Andalusian Network of Design and Translation of Advanced Therapies, 41092 Seville, Spain"},{"name":"Dermatology Department, School of Medicine, University of Granada, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3261-6745","authenticated-orcid":false,"given":"Raquel","family":"Sanabria-de la Torre","sequence":"additional","affiliation":[{"name":"Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain"},{"name":"Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain"},{"name":"Andalusian Network of Design and Translation of Advanced Therapies, 41092 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-1435","authenticated-orcid":false,"given":"Salvador","family":"Arias-Santiago","sequence":"additional","affiliation":[{"name":"Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain"},{"name":"Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain"},{"name":"Andalusian Network of Design and Translation of Advanced Therapies, 41092 Seville, Spain"},{"name":"Dermatology Department, School of Medicine, University of Granada, 18014 Granada, Spain"},{"name":"Dermatology Department, Virgen de las Nieves University Hospital, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jia, T., Qiao, W., Yao, Q., Wu, W., and Kaku, K. (2019). Treatment with docosahexaenoic acid improves epidermal keratinocyte differentiation and ameliorates inflammation in human keratinocytes and reconstructed human epidermis models. Molecules, 24.","DOI":"10.20944\/preprints201908.0178.v1"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.clindermatol.2013.05.021","article-title":"Basic histological structure and functions of facial skin","volume":"32","author":"Arda","year":"2014","journal-title":"Clin. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/wrr.12154","article-title":"The importance of both fibroblasts and keratinocytes in a bilayered living cellular construct used in wound healing","volume":"22","author":"Wojtowicz","year":"2014","journal-title":"Wound Repair Regen."},{"key":"ref_4","first-page":"1","article-title":"Effects of wound dressings containing silver on skin and immune cells","volume":"10","author":"Skoroplyas","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0213-005X(03)73008-0","article-title":"Cronolog\u00eda de la colonizaci\u00f3n bacteriana en grandes quemados: \u00bfEs el aislamiento estricto necesario?","volume":"21","author":"Barret","year":"2003","journal-title":"Enferm. Infecc. Microbiol. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1089\/wound.2016.0701","article-title":"The Role of Topical Antiseptic Agents Within Antimicrobial Stewardship Strategies for Prevention and Treatment of Surgical Site and Chronic Open Wound Infection","volume":"6","author":"Leaper","year":"2017","journal-title":"Adv. Wound Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1742-481X.2009.00639.x","article-title":"Wound cleansing, topical antiseptics and wound healing","volume":"6","author":"Atiyeh","year":"2009","journal-title":"Int. Wound J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"165","DOI":"10.7150\/jbji.26355","article-title":"Cytotoxicity evaluation of chlorhexidine gluconate on human fibroblasts, myoblasts, and osteoblasts","volume":"3","author":"Liu","year":"2018","journal-title":"J. Bone Jt. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Qui\u00f1ones-Vico, M.I., Fern\u00e1ndez-Gonz\u00e1lez, A., P\u00e9rez-Castej\u00f3n, E., Montero-V\u00edlchez, T., and Arias-Santiago, S. (2021). Cytotoxicity and Epidermal Barrier Function Evaluation of Common Antiseptics for Clinical Use in an Artificial Autologous Skin Model. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040642"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7435621","DOI":"10.1155\/2017\/7435621","article-title":"HaCaT Cells as a Reliable in Vitro Differentiation Model to Dissect the Inflammatory\/Repair Response of Human Keratinocytes","volume":"2017","author":"Colombo","year":"2017","journal-title":"Mediators Inflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1167\/tvst.5.2.17","article-title":"Titanium coating of the Boston keratoprosthesis","volume":"5","author":"Jeong","year":"2016","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"324","DOI":"10.5115\/acb.19.009","article-title":"Influence of traditional medicines on the activity of keratinocytes in wound healing: An in-vitro study","volume":"52","author":"Kotian","year":"2019","journal-title":"Anat. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Suarez-Arnedo, A., Figueroa, F.T., Clavijo, C., Arbel\u00e1ez, P., Cruz, J.C., and Mu\u00f1oz-Camargo, C. (2020). An image J plugin for the high throughput image analysis of in vitro scratch wound healing assays. PLoS ONE, 15.","DOI":"10.1101\/2020.04.20.050831"},{"key":"ref_14","first-page":"210","article-title":"Dilute Povidone-Iodine Solutions Inhibit Human Skin Fibroblast Growth","volume":"28","author":"Balin","year":"2002","journal-title":"Dermatol. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10561-017-9615-8","article-title":"Rapid preparation of a noncultured skin cell suspension that promotes wound healing","volume":"18","author":"Yoon","year":"2017","journal-title":"Cell Tissue Bank."},{"key":"ref_16","unstructured":"(2021, June 13). ClinicalTrials.gov ReCell\u00ae Combined With Meshed Skin Graft in the Treatment of Acute Burn Injuries, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02380612."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.ijsu.2017.06.073","article-title":"Povidone iodine in wound healing: A review of current concepts and practices","volume":"44","author":"Bigliardi","year":"2017","journal-title":"Int. J. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4103\/2321-3868.113331","article-title":"Collective cell migration: Implications for wound healing and cancer invasion","volume":"1","author":"Li","year":"2013","journal-title":"Burn. Trauma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s10561-017-9621-x","article-title":"Cytotoxicity testing of burn wound dressings: First results","volume":"18","author":"Koller","year":"2017","journal-title":"Cell Tissue Bank."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1097\/TA.0b013e31818b146d","article-title":"Mechanisms of delayed wound healing by commonly used antiseptics","volume":"66","author":"Thomas","year":"2009","journal-title":"J. Trauma-Inj. Infect. Crit. Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jss.2009.04.029","article-title":"Evaluation of toxic side effects of clinically used skin antiseptics in vitro","volume":"164","author":"Hirsch","year":"2010","journal-title":"J. Surg. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1136\/bjo.2010.189407","article-title":"Povidone-iodine application induces corneal cell death through fixation","volume":"95","author":"Chou","year":"2011","journal-title":"Br. J. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/icvts\/ivy248","article-title":"Povidone-iodine results in rapid killing of thymic epithelial tumour cells through cellular fixation","volume":"28","author":"Lee","year":"2019","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3109\/01480545.2013.846364","article-title":"Povidone-iodine-induced cell death in cultured human epithelial HeLa cells and rat oral mucosal tissue","volume":"37","author":"Sato","year":"2014","journal-title":"Drug Chem. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4012\/dmj.2009-031","article-title":"Effects of high-dose major components in oral disinfectants on the cell cycle and apoptosis in primary human gingival fibroblasts in vitro","volume":"29","author":"Nomura","year":"2010","journal-title":"Dent. Mater. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1177\/0091270010372628","article-title":"Skin cleansers: The risks of chlorhexidine","volume":"51","author":"Sivathasan","year":"2011","journal-title":"J. Clin. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.burns.2019.12.008","article-title":"Implications of chlorhexidine use in burn units for wound healing","volume":"46","author":"Tornay","year":"2020","journal-title":"Burns"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2106\/JBJS.M.00313","article-title":"Selection of an optimal antiseptic solution for intraoperative irrigation: An in vitro study","volume":"96","author":"Gawlitta","year":"2014","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/iwj.13555","article-title":"Topical effect of benzalkonium bromide on wound healing and potential cellular and molecular mechanisms","volume":"18","author":"Zhang","year":"2021","journal-title":"Int. Wound J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s10266-019-00465-z","article-title":"Cytotoxic effects of a chlorhexidine mouthwash and of an enzymatic mouthwash on human gingival fibroblasts","volume":"108","author":"Coelho","year":"2020","journal-title":"Odontology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"344","DOI":"10.4103\/ejd.ejd_149_17","article-title":"Cytotoxicity of chlorhexidine and neem extract on cultured human gingival fibroblasts through fluorescence-activated cell sorting analysis: An in-vitro study","volume":"12","author":"Verma","year":"2018","journal-title":"Eur. J. Dent."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1742-481X.2007.00331.x","article-title":"Effects of pH-neutral, super-oxidised solution on human dermal fibroblasts in vitro","volume":"4","author":"Arias","year":"2007","journal-title":"Int. Wound J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/iwj.12625","article-title":"In vitro microbicidal, anti-biofilm and cytotoxic effects of different commercial antiseptics","volume":"14","author":"Robson","year":"2017","journal-title":"Int. Wound J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"742858","DOI":"10.3389\/fbioe.2021.742858","article-title":"Systematic Review of the Application of Perinatal Derivatives in Animal Models on Cutaneous Wound Healing","volume":"9","author":"Pichlsberger","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"643125","DOI":"10.3389\/fcell.2021.643125","article-title":"Current Advanced Therapies Based on Human Mesenchymal Stem Cells for Skin Diseases","volume":"9","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"979","DOI":"10.7150\/ijms.9139","article-title":"Cell therapy with human MSCs isolated from the umbilical cord wharton jelly associated to a PVA membrane in the treatment of chronic skin wounds","volume":"11","author":"Ribeiro","year":"2014","journal-title":"Int. J. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1097\/BRS.0000000000002224","article-title":"Povidone-iodine Solutions Inhibit Cell Migration and Survival of Osteoblasts, Fibroblasts, and Myoblasts","volume":"42","author":"Liu","year":"2017","journal-title":"Spine (Phila. Pa. 1976)."},{"key":"ref_38","first-page":"1","article-title":"Transforming growth factor \u03b2 plays an important role in enhancing wound healing by topical application of Povidone-iodine","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"106064","DOI":"10.1016\/j.ijantimicag.2020.106064","article-title":"Addressing the challenges in antisepsis: Focus on povidone iodine","volume":"56","author":"Barreto","year":"2020","journal-title":"Int. J. Antimicrob. Agents"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/9\/1395\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:57:39Z","timestamp":1760137059000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/9\/1395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,20]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["cells11091395"],"URL":"https:\/\/doi.org\/10.3390\/cells11091395","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,20]]}}}