Evaluation of the use of tacrolimus ointment for the prevention of hypertrophic scars in experimental model

Abstract

Background: Tacrolimus, for its activity on modulation of collagen production and fibroblast activity, may have a role in the prevention of hypertrophic scars. Objectives: Evaluate macroscopic, microscopic, metabolic, laboratory effects and side effects of the use of topical tacrolimus ointment, in different concentrations, in the prevention of hypertrophic scars. Methods: Twenty-two rabbits were submitted to the excision of 2 fragments of 1 cm of each ear, 4 cm apart, down to cartilage. The left ear of the animals was standardized as control and Vaseline applied twice a day. The right ear received tacrolimus ointment, at concentrations of 0.1% on the upper wound and 0.03% on the lower wound, also applied twice a day. Macroscopic, microscopic, laboratory criteria and the animals' weight were evaluated after 30 days of the experiment. Results: Wounds treated with tacrolimus, at concentrations of 0.1% and 0.03%, when compared to control, showed a lower average degree of thickening (p = 0.048 and p <0.001, respectively). The average of scar thickness and lymphocyte, neutrophil and eosinophil concentrations are lower in the treated wounds compared to the control (p <0.001, p=0.022, p=0.007, p=0.044, respectively). The mean concentration of lymphocytes is lower in wounds treated with a higher concentration of the drug (p=0.01). Study limitations: experiment lasted only 30 days. Conclusions: Tacrolimus at the 2 concentrations evaluated reduced the severity of inflammatory changes and positively altered the macroscopic aspect of the scar in the short term. Its use was shown to be safe, with no evidence of systemic or local adverse effects.

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

“…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 26–28 . 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.…”

“…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.…”

“…After treatment with FK506, peri‐follicular repigmentation has been observed, and thus, activation of melanocyte stem cells within the hair follicle bulge is a probable mechanism of action for this treatment method 24,25 . Tacrolimus has been previously studied in a rabbit ear model of HTS, but evaluation of repigmentation was not included 26–28 . To our knowledge, the effect of tacrolimus on repigmentation in HTS has yet to be studied.…”

Emerging and Novel Therapies for Keloids

“…50 Another study demonstrated the beneficial effects of topical tacrolimus ointment in preventing hypertrophic scars in rabbit models. 51 In an open-label pilot study, the majority of patients exhibited a decrement in induration, erythema, pruritus and tenderness after topical application of tacrolimus ointment (0.1%) twice a day for 12 weeks, yet no statistically significant benefits as a therapeutic agent were observed. 52 Another study showed the preventive role of topical tacrolimus against keloids in 25 patients after surgery.…”

A Systematic Review Comparing Animal and Human Scarring Models

“…A punch biopsy was the most common device used to make skin incisions, reported in 31 of the 35 studies. Four studies reported creating a circular incision but did not specify the type of device used (13)(14)(15)34). One study compared the scar result from using a biopsy device with a controlled thermal injury (18).…”