Skin Res Technol. 2020;00:1–9. | 1 wileyonlinelibrary.com/journal/srt 1 | INTRODUCTION Human in vivo skin damage models simulate different cutaneous conditions, and for this reason, they have been used as a substitute for the patients in the clinical trials. 1,2 Models have multiple uses, from the investigation of the changes in the damaged skin, mecha- nism of the skin damage and healing, kinetics of the skin recovery to effectiveness of different therapeutic agents. 2,3 Protocols for implementation of some models have been stan- dardized and reported in their specific guidelines, 2 but for the Received: 9 March 2020 | Revised: 17 June 2020 | Accepted: 25 June 2020 DOI: 10.1111/srt.12932 ORIGINAL ARTICLE Comparison of mechanical, chemical and physical human models of in vivo skin damage: Randomized controlled trial Dario Leskur 1 | Ivana Perišić 1 | Kristina Romac 1 | Helena Šušak 1 | Ana Šešelja Perišin 1 | Josipa Bukić 1 | Doris Rušić 1 | Nebojša Kladar 2 | Biljana Božin 2 | Darko Modun 1 © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1 Department of Pharmacy, University of Split School of Medicine, Split, Croatia 2 Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia Correspondence Darko Modun, Department of Pharmacy, University of Split School of Medicine, Soltanska 2, Split 21000, Croatia. Email: dmodun@mefst.hr Abstract Introduction: Human in vivo models of skin damage were often used in research of cutaneous disorders. The most commonly used models were tape-stripping as me- chanical, sodium lauryl sulphate-induced irritation as chemical and ultraviolet radia- tion as physical damage model. In regard to differences between models, they were expected to have different responses to damage and recovery, with unique skin pa- rameters’ changes over time. Objective: The aim was to compare skin parameters in three different skin damage models on the same anatomical location, with and without topical treatment. Methods: Four test sites on each forearm were randomly assigned to three skin dam- age models with the fourth sites on each forearm chosen as a control, undamaged site. Skin parameters were assessed using non-invasive methods. Results: Sodium lauryl sulphate irritation caused the strongest damage with delayed reaction to the irritant. Tape stripping leads to highest initial skin barrier disruption but afterwards it showed the fastest skin recovery. Ultraviolet radiation did not af- fect skin barrier function, but it elevated skin erythema and melanin level. Tested preparation did not lead to changes in measured parameters. Conclusion: The skin of the participants had different response to three skin damage models with distinct changes of skin parameters and recovery. The trial was registered at ClinicalTrials.gov under the identifier NCT03783819. KEYWORDS in vivo skin damage models, non-invasive methods, skin barrier recovery, sodium lauryl sulphate, tape stripping, ultraviolet radiation