A simple drug‐delivery microneedling technique modality successfully improves linear atrophic scars

Atrophic scars are white, dermal depressions, caused by the destruction of collagen fibers and decrease in epidermal cells, following inflammation after different types of trauma. They lead to significant physical, aesthetic and psychological barriers and their treatment remain a therapeutic challenge for dermatologists. Microneedling has been shown to improve scars by stimulating angiogenesis and neocolagenesis and the combination of anti‐fibrotic drugs could potentialize the results.


| INTRODUC TI ON
There is currently a lack of treatments for linear, atrophic scars, although they are relatively common following surgeries or trauma and they are associated with significant patient distress due to poor aesthetic or functional outcomes. 1Although several therapies are available to treat scars, techniques to treat linear, atrophic, achromic scars following trauma and surgery, with the amelioration of the scar depression and texture are still challenging. 1croneedling has been shown to improve scars due to stimulation of neocolagenesis, angiogenesis and by reorganizing fibrosis. 3e combination of microneedling and anti-fibrotic drugs could possibly potentialize the results. 2,4MMP® (Micro infusion of drugs in skin) is a recently described microneedling technique that can deliver drugs into the dermis, using a special tattoo machine. 2 We describe the successful treatment of 8 patients with mature, atrophic and achromic scars, caused by incisional wounds.Patients were submitted to 2 or 3 monthly sessions of 5-FU and microneedling in an in-office procedure.

| ME THODS
The study was approved by the Ethical Committee (CAEE 69201623.5.0000.5134).All patients were treated in the clinic of one of the authors (Dr.Gasques).

| Surgical technique
Skin was cleansed with chlorhexidine solution; topical anesthesia is applied covering the whole scar area (Dermomax®).0.5 mL of 5-Fluoracila (Faldfluor, 50 mg/mL) was poured into a sterile dappen dish; a Cheyenne® tattoo machine (MT.Derm -Germany, Anvisa -Brazilian Heath Ministry -80281110016), with a Liner of 7 linear needles (Anvisa 80281110015) was immersed into the dappen and microneedling with 120 Hz speed was performed directly on the scar.The treatment endpoint is uniform, pinpoint bleeding.Immediately after the procedure, occlusive dressing (Tegaderm®) was applied and left for 12 h covering the whole scar area.

| Patients
Eight adult patients (22-42 years, mean = 30.3years) with scars from 6 to 60 months (mean = 31 months), atrophic, achromic, caused by different types of trauma and on different anatomical areas (Table 1) were submitted to 2-3 monthly sessions of the microneedling technique described above, using 5-FU.Two out of 8 patients had scars caused by accidents (car accident and accident with a bottle) while 6 patients had surgical scars (Table 1).The main patient's complaints were visible scars, scar discoloration and uneven scars.Photographs were taken before and 2 months after the second session.A patient's Assessment Scale (Likert Scale) was given to all patients and two doctors 6 months after the last treatment session, when they were required to rate their impression on the treatment results (Figure 1).

| Statistical analyses
Analyzes of parametric (Pearson) and non-parametric (Spearman) correlations were performed to compare the scores of the evaluators with each other.Additionally, we search possible numerical explanatory variables (time of evolution and age) with the scores attributed by both patients and physicians significantly correlated with each other.
Additionally, an analysis in randomized blocks, considering the scores assigned by each evaluator, including the patient himself, as a block, was performed to assess whether the cause of the injury had any influence on the average of the assigned scores.This same analysis was performed with data from the medical evaluators only.

| RE SULTS
The 8 patients completed the study, with one male and 7 female patients.6 out of 8 patients received two sessions of Microneedling, while only two patients were treated with three sessions.The majority of the scars in this study were caused by surgery, the mean age of patients was 30.3 years and scars were located on different anatomical sites (face, thigs, abdomen, knee and breast).A marked improvement in scar pigmentation and texture were noted by the doctors, 2 months following the last session (Figure 2).The assessment of the treatment by patients, 6 months after the last treatment session, using the Lickert Scale, showed an overall satisfaction; 6 out of 8 patients rated the results with the best "very satisfied" score, while 2 rated as "satisfied" (Figure 1).Side-effects included pain during application, reported by all patients, and one patient had transitory post-inflammatory hyperpigmentation, that improved with topical 4% hydroquinone cream, following with total resolution after 8 weeks.The complete resolution of erythema and crusts took a maximum of 7 days after the procedure.
Table 1 shows that, of the quantitative variables, only the comparisons between physician 2's and the patient's assessment scores presented a significant correlation (p = 0.05).Thus, the variables age and evolution time were compared only with these evaluators more correlated with each other.The non-significant correlation between many quantitative variables may be due to the reduced sample size.
Table 2 shows that the type of injury influenced the average of the evaluation scores (p = 0.02) considering all the scores of evaluations by physicians and the patient himself.This trend persisted (p = 0.08) even when only the assessment scores of both physicians were considered.Considering the three joint evaluations, in general, injuries from surgery (orthopedic), trauma (car accident), surgery (syryngoma) and surgery (leg tumor) had better evaluation scores, all with averages of 2.00, than those from surgery (mammoplasty), which had an average score of 0.66.On the other hand, considering the evaluations of just both physicians, in general, injuries from trauma (car accident), surgery (syryngoma) and surgery (leg tumor) had better evaluation scores, all with averages of 2.00, than those from surgery (mammoplasty), which had an average score of 0.50.

| DISCUSS ION
We have shown that MMP® microneedling combined with 5-FU, when applied directly to the scar tissue, has led to a less visible resulting scar, by targeting both fibrosis and hypopigmentation, with a high degree of both physician and patient satisfaction.A larger, prospective study is now being conducted to evaluate the benefits of this technique in different types of atrophic scars.
In this study, we also showed that the assessment scores of at least one of the professionals with those of the patient had significant correlations with each other, which shows consistency between the qualitative assessment instruments.We also demonstrated that the cause of the injury can influence joint assessment scores (physicians plus patient) or those exclusive to professionals trained for the application, generating evidence that the cause of the injury can influence the treatment outcome itself.
We have found in this study that the outcome is related to the extent of the trauma.Contradicting Garg et al, 8 regardless of the cause of the injury, surgical incision or traumatic scar, the size of the injury was more important in the outcome.Wich can be explained by the longer operative time, more extensive surgery, resulting in more edema and worse outcome.
Wound healing is a complex physiological process to repair a tissue that has been injured; injured human skin does not regenerate, but instead, it is replaced by a scar, a fibrous tissue with collagen distribution, texture and elasticity different from the normal skin. 4The quality of the newformed scar depends upon several factors, such as anatomical site, skin color and age. 5 Several techniques have been used to improve acne scars, as well as hypertrophic scars, but there is currently a lack of studies to decrease the uneven and dyschromic aspect of linear scars. 1,7croneedling was described as a technique that could improve the fibrotic pattern of depressed scars.It promotes small punctate lesions that cross the epidermis and dermis, leading to columns filled with blood, evolving with inflammation, fibroblast proliferation and neocollagenesis. 65-FU is an antineoplastic agent that induces fibroblast apoptosis and inhibits TGF-b1 and type I collagen production, by fibroblats. 2 It has been widely used as a safe and effective intralesional therapy to potentialize the effects of triamcinolone to treat keloids and hypertrophic scars, 7,9 and it also improves skin color in pigmentary disorders, such as guttate idiopatic hypomelanosis 8,10 and vitiligo, 10 possibly by stimulating the secretion of CXCL12 by dermal fibroblasts. 11croneedling improves scars due to stimulation of neocollagenesis, angiogenesis and by reorganizing fibrosis.5-FU has been widely shown to have a benefit to treat hypertrophic and retractile results.
The combination of microneedling and anti-fibrotic drugs can potentialize the results. 2 The recent development of a technique that uses a tattoo machine to deliver drugs into the skin has appeared as a new method, with the advantages of being inexpensive and easily done as an in-office procedure. 2,4,5gardless of the etiology, all scars showerd some degree of improvement with the treatment.F I G U R E 2 Linear atrophic scars with hypopigmentation and irregular surface.Located on the lower eyelid (A), upper lip (B) and lateral area of the thigh (C) were treated using two sessions of MMP® and drug delivery of 5-FU.The scar on the thigh followed with hyperpigmentation, with complete improvement after 8 weeks (C).

F I G U R E 1
Lickert Scale given to doctors and patients.TA B L E 2 Association between type of lesion and evaluation scores.