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Nakamoto et al. Plast Aesthet Res 2024;11:54  https://dx.doi.org/10.20517/2347-9264.2024.82  Page 13 of 14

               The present study has several limitations. First, it did not explore possible mechanisms by which the beta-
               blocker accelerated the epithelialization in grafted wounds. Second, the study lasted only 14 days, which
               limited the evaluation of cosmetic outcomes and scar contracture. Third, a dose-dependency study for
               timolol was not conducted to determine the optimal concentration. Fourth, the study did not assess the
               protein levels (post-transcriptional level) of the measured markers. Finally, RNA levels of these markers
               were only measured on Day 14, leaving their potential changes at early time points unexamined. Therefore,
               studies are needed to investigate the mechanistic aspects of the beneficial effects of beta-blockers in wound
               healing.

               DECLARATIONS
               Authors’ contributions
               Developed the concept and planned the experiments: Nakamoto K, Enkhbaatar P
               Carried out the experiments: Nakamoto K, Batsaikhan TA, Kakizaki R, Heathman T
               Contributed to RT-qPCR analysis: Liu N, Fagg WS
               Provided critical feedback and helped analyze data and prepare the manuscript: Nakamoto K, Batsaikhan
               TA, Liu N, Fagg WS, Kakizaki R, Heathman T, Enkhbaatar P


               Availability of data and materials
               The data that support the findings of this study are available from the corresponding author, Nakamoto K,
               upon reasonable request.

               Financial support and sponsorship
               Financial support for Nakamoto K, Batsaikhan TA, Kakizaki R, Heathman T, and Enkhbaatar P was
               National Institutes of Health GM097480. Funding support for Fagg WS and Liu N was from the John L
               Hern University Chair in Transplant Surgery to Fagg WS and the Mimmie and Hallie Smith Endowed
               Chair of Transplant Research to Fagg WS.

               Conflicts of interest
               All authors declared that there are no conflicts of interest.

               Ethical approval and consent to participate
               This study followed the guidelines of the National Institutes of Health and the American Physiological
               Society regarding the care and use of laboratory animals, and the protocol of this study was approved by the
               University of Texas Medical Branch Animal Care and Use Committee (protocol #2003030).


               Consent for publication
               Not applicable.

               Copyright
               © The Author(s) 2024.


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