Tacrolimus action pathways in an ointment base for hypertrophic scar prevention in a rabbit ear model

Menezes, Mariana Campos Souza; Buzelin, Marcelo Araújo; Nunes, Cristiana Buzelin; Alberti, Luiz Ronaldo

doi:10.1016/j.abd.2020.08.019

Cited by 6 publications

(9 citation statements)

References 32 publications

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“…No significant difference in VEGF expression, which has been previously found to be elevated in HTS, 37,38 between treatment and control groups was found. However, wounds treated with 0.1% tacrolimus had less dense, more organized, and finer collagen fibers, as well as more organized and denser elastic fibers 27 . These studies evaluated the use of tacrolimus in preventing HTS formation by beginning treatment on the same day as wound creation in contrast to the current study where HTSs were allowed to form before treatment.…”

Section: Discussionmentioning

confidence: 90%

“…Both topical and intradermal tacrolimus treatment have been previously studied in HTSs using rabbit ear models, but their effects on pigmentation were not measured, and the model itself does not lend itself to the study of high FST skin. [26][27][28] Menezes et al and Gisquet et al both found a reduction in scar thickness and inflammatory cellular density in scars treated with tacrolimus compared to controls. 26,28 Immunohistochemical analysis of excised wounds after 30 days of 0.1% or 0.03% topical tacrolimus treatment showed decreased transforming growth factor-b, a well-known contributor to fibrosis in HTS, and smooth muscle actin expression.…”

Section: Discussionmentioning

confidence: 97%

“…However, wounds treated with 0.1% tacrolimus had less dense, more organized, and finer collagen fibers, as well as more organized and denser elastic fibers. 27 These studies evaluated the use of tacrolimus in preventing HTS formation by beginning treatment on the same day as wound creation in contrast to the current study where HTSs were allowed to form before treatment. However, Shen et al recently used tacrolimus to treat HTSs that were formed in a rabbit ear model, and showed downregulatory effects of tacrolimus on angiogenic factors in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Tacrolimus has been previously studied in a rabbit ear model of HTS, but evaluation of repigmentation was not included. [26][27][28] To our knowledge, the effect of tacrolimus on repigmentation in HTS has yet to be studied. If proven to be safe and efficacious, tacrolimus would provide a noninvasive method of promoting pigmentation hence relieving morbidity associated with dyschromic burn scars.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of hypopigmented burn hypertrophic scars with short‐term topical tacrolimus does not lead to repigmentation

Molina,

Travis,

Hussein

et al. 2024

Lasers Surg Med

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ObjectivesDyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls.MethodologyFull‐thickness burns in red Duroc pigs were either treated with excision and meshed split‐thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO2 laser treatment before topical tacrolimus application to induce laser‐assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin‐fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis‐related genes: Tyrosinase (TYR), TYR‐related protein‐1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Šídák's multiple comparisons test was used to compare groups.ResultsOver time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the −Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (−Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (−Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non‐LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment.ConclusionHypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Treatment of hypopigmented burn hypertrophic scars with short‐term topical tacrolimus does not lead to repigmentation

Molina,

Travis,

Hussein

et al. 2024

Lasers Surg Med

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“…Tacrolimus (0.1%) had a potent inhibitory effect on smooth muscle actin and can reduce the density of collagen fibers scars with the alleviation of scar inflammation even at the concertation of 0.03% tacrolimus. Tacrolimus could effectively inhibit TGF-β Smooth muscle actin, reduce mucin, and enhance collagen fiber quality and elastic fiber density ( Menezes et al, 2021 ).…”

Section: Therapeutic Methods For Hsmentioning

confidence: 99%

Traditional Chinese medicine for hypertrophic scars—A review of the therapeutic methods and potential effects

Chen

Zhang

et al. 2022

Front. Pharmacol.

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Hypertrophic scar (HS) is a typical pathological response during skin injury, which can lead to pain, itching, and contracture in patients and even affect their physical and mental health. The complexity of the wound healing process leads to the formation of HS affected by many factors. Several treatments are available for HS, whereas some have more adverse reactions and can even cause new injuries with exacerbated scarring. Traditional Chinese Medicine (TCM) has a rich source, and most botanical drugs have few side effects, providing new ideas and methods for treating HS. This paper reviews the formation process of HS, the therapeutic strategy for HS, the research progress of TCM with its relevant mechanisms in the treatment of HS, and the related new drug delivery system of TCM, aiming to provide ideas for further research of botanical compounds in the treatment of HS, to promote the discovery of more efficient botanical candidates for the clinical treatment of HS, to accelerate the development of the new drug delivery system and the final clinical application, and at the same time, to promote the research on the anti-HS mechanism of multiherbal preparations (Fufang), to continuously improve the quality control and safety and effectiveness of anti-HS botanical drugs in clinical application.

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Development of a Tacrolimus-loaded carboxymethyl chitosan scaffold as an effective 3D-printed wound dressing

Al-Hashmi,

Vakilian,

Jamshidi-adegani

et al. 2023

Journal of Drug Delivery Science and Technology

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Tacrolimus action pathways in an ointment base for hypertrophic scar prevention in a rabbit ear model

Cited by 6 publications

References 32 publications

Treatment of hypopigmented burn hypertrophic scars with short‐term topical tacrolimus does not lead to repigmentation

Treatment of hypopigmented burn hypertrophic scars with short‐term topical tacrolimus does not lead to repigmentation

Traditional Chinese medicine for hypertrophic scars—A review of the therapeutic methods and potential effects

Development of a Tacrolimus-loaded carboxymethyl chitosan scaffold as an effective 3D-printed wound dressing

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