{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:01:40Z","timestamp":1789970500828,"version":"4.0.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Topical antiseptics must control wound bioburden without damaging cells required for tissue repair, yet cytocompatibility data obtained from isolated active compounds or monolayer exposure may not reflect finished formulations under clinically relevant conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study compared the cytotoxic effects of six commercial antiseptics and wound-irrigation solutions across complementary\n                      <jats:italic>in-vitro<\/jats:italic>\n                      and\n                      <jats:italic>ex-vivo<\/jats:italic>\n                      models. An octenidine-based antiseptic, two polyhexamethylene biguanide formulations (0.1 and 0.04%) and three chlorine-based solutions (0.005% sodium hypochlorite\/hypochlorous acid, 0.08% sodium hypochlorite, and 0.03% hypochlorous acid) were tested in HaCaT keratinocytes and CRL-2522 human dermal fibroblasts. Cell viability was assessed after 24 h using an ISO 10993-5-based assay and after 1, 5 and 15 min using an application-oriented exposure-and-washout assay. In addition, the cell viability and membrane integrity was assessed by a qualitative LIVE\/DEAD staining. Repeated topical treatment was additionally evaluated over 15 days in a human full-thickness\n                      <jats:italic>ex-vivo<\/jats:italic>\n                      skin wound model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cytotoxicity was strongly dependent on formulation, exposure time, concentration, and cell type. Octenidine\/Phenoxyethanol caused the greatest and most rapid loss of viability, with substantial effects after 1 min and the most pronounced epithelial disorganization\n                      <jats:italic>ex-vivo<\/jats:italic>\n                      . Both polyhexamethylene biguanide formulations showed cytotoxicity during continuous 24 h exposure and, despite better short-term tolerance, impaired epithelial continuity after repeated treatment. The 0.005% sodium hypochlorite\/hypochlorous acid and 0.08% sodium hypochlorite formulations maintained viability above the 70% cytotoxicity threshold under all tested conditions and preserved epithelial architecture. The 0.03% hypochlorous acid formulation showed time-, concentration-and cell-specific toxicity, including marked keratinocyte damage after 15 min in LIVE\/DEAD analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Cytocompatibility cannot be inferred from antiseptic class or nominal active-agent concentration alone. Finished formulations should be evaluated across various clinically relevant exposure conditions and tissue-level models and product selection should balance antimicrobial efficacy with preservation of regenerative cells and tissue.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1945836","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:36:17Z","timestamp":1789968977000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytotoxicity of antimicrobial wound irrigation solutions and antiseptics: an in vitro and ex vivo study"],"prefix":"10.3389","volume":"17","author":[{"given":"Sophie Charlotte","family":"Liegenfeld","sequence":"first","affiliation":[{"name":"Department for Vascular Medicine, Translational Wound Research, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf (UKE)","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Krueger","sequence":"additional","affiliation":[{"name":"Department for Vascular Medicine, Translational Wound Research, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf (UKE)","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Severing","sequence":"additional","affiliation":[{"name":"MEDICE Arzneimittel P\u00fctter GmbH & Co. KG","place":["Iserlohn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Dittmer","sequence":"additional","affiliation":[{"name":"Department for Vascular Medicine, Translational Wound Research, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf (UKE)","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa K.","family":"Stuermer","sequence":"additional","affiliation":[{"name":"Department for Vascular Medicine, Translational Wound Research, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf (UKE)","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian-Dario","family":"Rembe","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf (HHU)","place":["D\u00fcsseldorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4792","DOI":"10.1038\/s41598-020-61728-2","article-title":"Efficacy of antiseptics in a novel 3-dimensional human plasma biofilm model (hpbiom)","volume":"10","author":"Besser","year":"2020","journal-title":"Sci. Rep."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1111\/ddg.15649","article-title":"Systematics, diagnosis and treatment of wound infections in chronic wounds: a position paper from Wunddach","volume":"23","author":"Dissemond","year":"2025","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"477","DOI":"10.12968\/jowc.2014.23.10.477","article-title":"Antimicrobials and Non-Healing Wounds. Evidence, controversies and suggestions-key messages","volume":"23","author":"Gottrup","year":"2014","journal-title":"J Wound Care"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1111\/wrr.12387","article-title":"Epidemiology of chronic wounds in Germany: analysis of statutory health insurance data","volume":"24","author":"Heyer","year":"2016","journal-title":"Wound Repair Regen."},{"key":"ref5","doi-asserted-by":"publisher","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":"ref6","doi-asserted-by":"publisher","first-page":"139","DOI":"10.4414\/smw.2007.11434","article-title":"Effect of polyhexanide and gentamycin on human osteoblasts and endothelial cells","volume":"137","author":"Ince","year":"2007","journal-title":"Swiss Med. 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Surg."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1111\/iwj.13336","article-title":"Influence of human wound exudate on the bactericidal efficacy of antiseptic agents in quantitative suspension tests on the basis of European standards (din En 13727)","volume":"17","author":"Radischat","year":"2020","journal-title":"Int. Wound J."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"700","DOI":"10.3390\/biom11050700","article-title":"Immunology of acute and chronic wound healing","volume":"11","author":"Raziyeva","year":"2021","journal-title":"Biomolecules"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1099\/jmm.0.000294","article-title":"Comparing two polymeric biguanides: chemical distinction, antiseptic efficacy and cytotoxicity of polyaminopropyl biguanide and polyhexamethylene biguanide","volume":"65","author":"Rembe","year":"2016","journal-title":"J. Med. Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"564513","DOI":"10.3389\/fmicb.2020.564513","article-title":"Antimicrobial Hypochlorous wound irrigation solutions demonstrate lower anti-biofilm efficacy against bacterial biofilm in a complex in-vitro human plasma biofilm model (hpbiom) than common wound antimicrobials","volume":"11","author":"Rembe","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/5584_2021_645","article-title":"Antibiofilm efficacy of Polihexanide, Octenidine and sodium hypochlorite\/Hypochlorous acid based wound irrigation solutions against Staphylococcus aureus, Pseudomonas aeruginosa and a multispecies biofilm","volume":"1369","author":"Salisbury","year":"2022","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s12879-017-2220-4","article-title":"Proposed phase 2\/ step 2 in-vitro test on basis of En 14561 for standardised testing of the wound antiseptics Pvp-iodine, chlorhexidine digluconate, polihexanide and octenidine dihydrochloride","volume":"17","author":"Schedler","year":"2017","journal-title":"BMC Infect. Dis."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1111\/wrr.12590","article-title":"Consensus guidelines for the identification and treatment of biofilms in chronic nonhealing wounds","volume":"25","author":"Schultz","year":"2017","journal-title":"Wound Repair Regen."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1177\/21621918251359554","article-title":"Human wound and its burden: updated 2025 compendium of estimates","volume":"14","author":"Sen","year":"2025","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2751","DOI":"10.3390\/biomedicines10112751","article-title":"Composition of challenge substance in standardized antimicrobial efficacy testing of wound antimicrobials is essential to correctly simulate efficacy in the human wound Micro-environment","volume":"10","author":"Severing","year":"2022","journal-title":"Biomedicine"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1093\/jac\/dky432","article-title":"Safety and efficacy profiles of different commercial sodium hypochlorite\/hypochlorous acid solutions (NaClO\/HclO): antimicrobial efficacy, cytotoxic impact and physicochemical parameters in vitro","volume":"74","author":"Severing","year":"2019","journal-title":"J. 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Health"},{"key":"ref26","first-page":"e5","article-title":"Hypochlorous acid as a potential wound care agent: part I. Stabilized hypochlorous acid: a component of the inorganic armamentarium of innate immunity","volume":"6","author":"Wang","year":"2007","journal-title":"J. Burns Wounds"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1111\/wrr.12528","article-title":"Antibacterial activity of polihexanide formulations in a co-culture of HaCaT keratinocytes and Staphylococcus aureus and at different pH levels","volume":"25","author":"Wiegand","year":"2017","journal-title":"Wound Repair Regen."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1945836\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:36:17Z","timestamp":1789968977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1945836\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":27,"alternative-id":["10.3389\/fmicb.2026.1945836"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1945836","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"article-number":"1945836"}}