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Nakamoto et al. Plast Aesthet Res 2024;11:54 Plastic and
DOI: 10.20517/2347-9264.2024.82
Aesthetic Research

Original Article Open Access

Topical application of beta-blockers accelerates
epithelialization to mesh skin grafted full-thickness

burn in sheep

4
3
1
Kan Nakamoto 1,2 , Tsend Ayush Batsaikhan , Naiyou Liu , W. Samuel Fagg 4,5 , Ryuichiro Kakizaki ,
1
Thomas Heathman , Perenlei Enkhbaatar 1
1
Department of Anesthesiology, University of Texas Medical Branch Galveston, Galveston, TX 77555, USA.
2
Department of Plastic and Reconstructive Surgery, Tokyo Women’s Medical University, Tokyo 162-0056, Japan.
3
Department of Surgery, University of Texas Medical Branch Galveston, Galveston, TX 77555, USA.
4
Transplant Division, Department of Surgery, University of Texas Medical Branch Galveston, Galveston, TX 77555, USA.
5
Merakris Therapeutics RTP Frontier 800 Park Offices Dr. Suite 3322, Research Triangle Park, Durham, NC 27709, USA.
Correspondence to: Dr. Kan Nakamoto, Dr. Perenlei Enkhbaatar, Department of Anesthesiology, University of Texas Medical
Branch Galveston, 301 University Blvd, Galveston, TX 77555, USA. E-mail: kanakamo@utmb.edu; nakamoto.kan@twmu.ac.jp;
peenkhba@utmb.edu
How to cite this article: Nakamoto K, Batsaikhan TA, Liu N, Fagg WS, Kakizaki R, Heathman T, Enkhbaatar P. Topical application
of beta-blockers accelerates epithelialization to mesh skin grafted full-thickness burn in sheep. Plast Aesthet Res 2024;11:52.
https://dx.doi.org/10.20517/2347-9264.2024.82
Received: 10 Jun 2024 First Decision: 18 Sep 2024 Revised: 4 Oct 2024 Accepted: 15 Oct 2024 Published: 31 Oct 2024

Academic Editor: Xianwen Wang Copy Editor: Ting-Ting Hu Production Editor: Ting-Ting Hu

Abstract
Aim: Beta-adrenergic receptor blockers are conventionally used for the treatment of hypertension, tachycardia, and
glaucoma. Research has shown that beta-blockers can accelerate wound epithelialization. In this study, we tested
the efficacy of the beta-blocker timolol in an ovine model of grafted full-thickness burn wound healing, which
closely mimics clinical scenarios.

Methods: Six full-thickness burn wounds were created on the sheep’s posterior surface. Twenty-four hours later,
eschars were excised and meshed skin was grafted (Day0). The wounds in the treatment group received topical
application of timolol. Blood flow was measured using a blood perfusion imager. Cardiovascular hemodynamics
and blood glucose levels were recorded daily. The epithelialization rate on Day 14 was determined by planimetric
assay and analyzed by paired t-test. The days that the epithelialization rate exceeded 85%, 90%, and 95% were
analyzed by survival analysis. To assess the potential influence of TGFβ, epithelial-mesenchymal transition (EMT),
or myofibroblast activation (MFA) on wound healing, the RNA abundance of gene products related to these

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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