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. 2023 May 25;29(6):e13353. doi: 10.1111/srt.13353

Split‐face evaluation: Gluconolactone plus oxybrasion versus gluconolactone plus microneedling. The effects on skin parameters

Sylwia Jarząbek‐Perz 1,, Marta Dziedzic 1, Anna Kołodziejczak 1, Helena Rotsztejn 1
PMCID: PMC10209840  PMID: 37357656

Abstract

Background

The application of polyhydroxy acids and alpha‐hydroxy acids to the skin is often used in cosmetology. To enhance the effect of gluconolactone chemical peeling, a combined method including water‐oxygen oxybrasion or microneedle mesotherapy can be used.

Objectives

To evaluate skin parameters such as hydration, sebum, pH and TEWL after application of a 10% gluconolactone chemical peel in combination with oxybrasion and microneedling.

Materials and methods

Twenty‐one Caucasian women participated in the study. A series of three split face treatments was carried out at 1‐week intervals. Oxybrasion was performed on the right side of the face and micro‐needle mesotherapy on the left side. A 10% gluconolactone solution was applied to the entire face. Before the first and third treatments and 2 weeks after the last treatment, skin parameters were evaluated. Photographic documentation was also made before and after the treatment series.

Results and conclusion

Evaluation of skin parameters using Courage & Khazaka 580 Multi Probe Adapter probes (Courage + Khazaka electronic GmbH, Cologne, Germany) showed an increase in hydration and a decrease in sebum, pH and TEWL for both treatments. There were no statistically significant differences between the treatments. Combining chemical peeling of gluconolactone with oxybrasion and microneedle mesotherapy is a good method to seal the hydrolipid barrier and increase skin hydration.

Keywords: gluconolactone, hydration, microdermabrasion, microneedling, oxybrasion, pH, sebum, skin parameters, TEWL

1. INTRODUCTION

Skin parameters like hydration, transepidermal water loss (TEWL), pH, and sebum levels illustrate the functioning of the epidermal barrier. Evaluation of skin parameters provides the basis for selecting appropriate treatments and testing their effectiveness. 1

Combination treatments have been performed more and more frequently in cosmetology to increase their effects and achieve better results. One of such treatments is the combination of mechanical exfoliation with microdermabrasion and the application of chemical peels on the skin. 2 , 3 , 4 Many researchers describe the effect of corundum or diamond microdermabrasion and alpha hydroxy acids and polyhydroxy acids, such as lactobionic acid. 3 , 4 An interesting combination seems to be the use of another type of microdermabrasion—oxybrasion and chemical peeling of gluconolactone. These treatments are noninvasive, they are also time effective, safe and suitable for all types of skin. 5 , 6

Oxybrasion is also known as oxygen or water‐oxygen microdermabrasion. It is a procedure for superficial exfoliation of the epidermis, during which a biphasic stream composed of Natrium Chloratum (9% NaCl) and compressed oxygen is applied to the skin using a special head. Oxybrasion has a moisturizing effect, stabilizes sebaceous glands, and stimulates and increases blood circulation, resulting in better nutrition and oxygenation of tissues. Controlled exfoliation of the superficial layers of the epidermis facilitates the penetration of active substances. Due to the use of sodium chloride solution and pure oxygen from the cylinder, the destruction of the anaerobic environment occurs and thus the elimination of anaerobic Cutibacterium acnes bacteria. As a result, tissue regeneration is accelerated and skin inflammation is reduced. Water‐oxygen microdermabrasion is also characterized by high hygiene since the head does not directly touch the patient's skin. The efficacy of the treatment depends on the pressure selected and the number of repetitions. 2 , 5 , 7 , 8

Gluconolactone (GLA) is a relatively new cosmetic ingredient that combines the properties of glucose (reduces diffusion and evaporation of water from the epidermis) and alpha‐hydroxy acids. 9 It is also similar to polyhydroxy acids: it does not cause irritation, redness or burning. Gluconolactone increases skin hydration, has antiacne, soothing and antiaging properties; it protects elastin fibers from the degrading effects of ultraviolet radiation. GLA forms a delicate film on the surface of the skin, thus reducing TEWL, so it is used as a regenerative substance after invasive procedures. 6 , 10 , 11 , 12 , 13

In addition to microdermabrasion, another way to increase the penetration of active substances is undoubtedly micro‐needle mesotherapy. Mechanical puncturing of the skin with thin needles interrupts its continuity, creating channels to introduce desired substances, such as vitamin C, retinoids, platelet‐rich plasma or chemical peels. 14 , 15 , 16 , 17 Micro‐needle mesotherapy can be performed with dermarollers and dermapen. The dermapen punctures the skin with pulsatile, automatic movement of the needles directed perpendicularly to the skin surface. Depending on the area treated, it is possible to select the appropriate depth (0.25–2.5mm) and the ejection speed. 14 A depth setting of 0.15mm results in accumulation of the active ingredient in the stratum corneum, while as little as 0.5 mm allows transdermal penetration. 14 , 18

The purpose of this work was to examine skin parameters such as hydration, sebum, TEWL, and pH before, during and after a series of split‐face treatments using oxybrasion plus gluconolactone and microneedling plus gluconolactone, and to compare the effectiveness of the two procedures.

2. MATERIALS AND METHODS

2.1. Participants

The study included 21 Caucasian female subjects aged 39 to 62 years, with skin classified as phototype II and III on the Fitzpatrick scale. Contraindications to the procedure were active herpes, bacterial, viral, fungal diseases of the facial skin, pregnancy, lactation, psoriasis, retinoid therapy and up to six months and after completion, oral and topical antibiotic therapy that causes skin thinning and irritation, freshly tanned skin, susceptibility to hypertrophic scars and keloids, generally poor health condition.

The subjects surveyed had no contraindications to the treatments. They were asked to refrain from other cosmetic and dermatological procedures for the duration of the study. Approximately 6 h before scheduled treatment, subjects were asked to stop using any cosmetic products. The study participants were instructed about the procedure and perioperative care.

2.2. Evaluation of skin parameters

The study evaluated skin parameters such as hydration, sebum, pH, and TEWL. The measurement sites on both sides of the face were forehead, cheeks, nose (due to the high sensitivity of the tewameter probe, this parameter was not measured on the nose) and the eye area (Figure 1).

FIGURE 1.

FIGURE 1

Location of the studied areas including performed treatments.

The skin parameters were measured before the first and third treatments and two weeks after the last treatment (six weeks after the first treatment). Assessments were carried out according to the EEMCO guidelines. All measurements were taken in the same room, with constant temperature (24–26°C) and humidity (33%–41%), always at similar times of the day, after a 15 min acclimatization. Each measurement was taken three times at the same site, and then the average was drawn. The evaluations were made using the Courage & Khazaka 580 Multi Probe Adapter probes (Courage + Khazaka electronic GmbH, Cologne, Germany): Corneometer CM 825 (measures stratum corneum hydration), Sebumeter SM 815 (measures the amount of sebum secreted), pH‐Meter PH 905 (measures pH), Tewameter TM 300 (measures TEWL or transepidermal water loss from the epidermis).

2.3. Photographic documentation

Before starting the series of treatments and two weeks after the last procedure, the study subjects were photographed using the Fotomedicus system (Elfo).

2.4. Procedures

All participants underwent a series of three treatments applied at one‐week intervals. After cleansing the facial skin and disinfecting with Octenisept, the treatments were performed using the split‐face method: oxygen microdermabrasion was performed on the right side of the face and micro‐needle mesotherapy on the left side. Then a 10% gluconolactone chemical peel solution (INCI: Aqua, glucose delta‐lactone, pH = 2,3, product manufactured by CHANTARELLE Laboratory Derm Aesthetics) was applied to the entire face. The oxybrasion was performed using a Criss Hydroxy device, with the head placed approximately 0.5 cm from the skin at a pressure setting of 4.5–5.5 bar, depending on the skin and the treatment area. For microneedling, the Derma N‐Skin Pen Symbiosis device disposable sterile cartridges with 18 surgical steel needles were used. Both procedures were performed starting from the forehead, through the eye area, cheeks, chin, nose, and around the mouth, in vertical and horizontal planes. Since oxybrasion is a gentle procedure, three passes with the head were performed. Gluconolactone does not require neutralization; therefore, the product was washed off with lukewarm water.

The study was carried out according to the principles of the Declaration of Helsinki and was approved by the Ethics Committee. All participants gave their informed consent to participate in the study and to publish photographic documentation.

2.5. Statistical analysis

The IBM SPSS Statistics 27 program was used for statistical analysis. A value of 0.05 was used as the level of significance. The Shapiro‐Wilk test was chosen to test whether the data were normally distributed. A group of nonparametric tests for dependent variables was chosen to analyze differences in data distributions between groups: the Wilcoxon rank sum test and the Friedman analysis of variance. The Bonferroni test was chosen as the post hoc test.

3. RESULTS

3.1. Hydration

The Corneometer test on the left side showed that there was a significant difference in moisture levels for all the measurement sites. For the forehead, nose, and cheek, the moisture level for the first measurement was significantly lower than for the second and third ones. In the case of the eye area, in particular, the moisture level for the first measurement was the lowest, while there were no significant differences between the second and third measurements.

For the right side, where the chemical peel of gluconolactone with oxybrasion treatment was performed, the hydration level for the forehead, nose and eye areawas shown to increase with each treatment and was highest during the third measurement. For the cheek, no significant differences were observed between the first and second measurements; only during the third measurement was a significant increase in epidermal hydration. The results are presented in the diagrams (Figure 2).

FIGURE 2.

FIGURE 2

Assessment of the (A) forehead, (B) cheek, (C) nose, (D) eye area hydration using Corneometer. Skin parameters were measured before the first (L1,R1) and fourth (L2,R2) treatments and 2 weeks after the last treatment (L3,R3). L – left side (microneedling plus 10% gluconolactone), R – right side (oxybrasion plus 10% gluconolactone).

3.2. Sebum

Statistical analysis of the sebumeter measurements showed that the sebum secretion level on the left side for the forehead, eye area, and nose was lowest for the third measurement, that is, after the treatment series was completed. Also on the cheek, a significant difference was found only in the third measurement, and the result was significantly lower than before the beginning of the treatment series.

On the right side, sebum levels on the forehead, nose, and eye area were significantly lower for the third measurement. No statistically significant differences were observed between the first and second measurements. On the cheek, the sebum levels for the first measurement were significantly higher than for the second and third measurements (Figure 3).

FIGURE 3.

FIGURE 3

Assessment of the (A) forehead, (B) cheek, (C) nose, (D) eye area sebum using Sebumeter. Skin parameters were measured before the first (L1,R1) and fourth (L2,R2) treatments and 2 weeks after the last treatment (L3,R3). L – left side (microneedling plus 10% gluconolactone), R – right side (oxybrasion plus 10% gluconolactone).

3.3. pH

Statistical analysis showed significant differences in pH values for all measurement sites on both sides of the face. The obtained results are presented in the diagrams (Figure 4). On both the left and right sides on the forehead, nose, cheek and eye area, pH levels decreased with each treatment.

FIGURE 4.

FIGURE 4

Assessment of the (A) forehead, (B) cheek, (C) nose, (D) eye area pH using pH‐Meter. Skin parameters were measured before the first (L1,R1) and fourth (L2,R2) treatments and 2 weeks after the last treatment (L3,R3). L – left side (microneedling plus 10% gluconolactone), R – right side (oxybrasion plus 10% gluconolactone).

3.4. TEWL

For the parameter of transepidermal water loss with microneedling treatments combined with gluconolactone, significant differences were observed on the forehead, cheek, and eye area. At the aforementioned measurement sites, the TEWL level for the first measurement was significantly higher than that for the second and third measurements. There were no statistically significant differences between the second and third measurements on the forehead. The results are presented in the graphs (Figure 5).

FIGURE 5.

FIGURE 5

Assessment of the (A) forehead, (B) cheek, (C) nose, (D) eye area transepidermal water loss (TEWL) using Tewameter. Skin parameters were measured before the first (L1,R1) and fourth (L2,R2) treatments and 2 weeks after the last treatment (L3,R3). L – left side (microneedling plus 10% gluconolactone), R – right side (oxybrasion plus 10% gluconolactone).

The TEWL level for the right side of the forehead and the eye area did not change during the first two measurements, while a significant decrease in this parameter was found for the third measurement, that is, after the end of the treatment series. For the cheek, the decrease in TEWL was significantly noticeable at the second measurement, and the level was also maintained at the last measurement.

3.5. Comparision of treatments

After the treatment series, between the sites there were no statistically significant differences in measurements for most of the parameters and almost all the measurement sites. It was observed that there was a significant difference between the right and left sides of TEWL for the eye. The decreases in the TEWL values for the left side were significantly greater than the decreases in TEWL values for the right side. Statistical analysis of the studied parameters according to the site before, during and after the series of treatments is shown in Tables 1 and 2.

TABLE 1.

Statistical analysis of the studied parameters according to the site before, during, and two weeks after the series of micro‐needle mesotherapy treatments with 10% gluconolactone.

Friedman's variance analysis
Measurement Mean value Median SD Min Max Statistics p‐Value
Hydration Forehead 1 50.43 50.60 10.548 19.60 72.00 35.735 <0.001
2 57.19 55.43 8.391 46.01 79.00
3 61.92 59.54 8.342 49.90 81.50
Nose 1 26.03 23.40 11.619 11.20 49.50 36.169 <0.001
2 33.30 32.73 10.281 14.20 55.00
3 43.02 42.53 11.772 15.40 65.10
Cheek 1 40.95 42.80 13.369 9.00 66.80 32.667 <0.001
2 48.08 47.90 12.594 7.90 72.00
3 53.60 52.30 11.387 19.30 72.53
Eye area 1 48.74 46.30 11.392 23.23 69.00 27.928 <0.001
2 57.02 56.30 11.597 27.45 75.70
3 60.64 64.90 11.455 35.60 78.30
Sebum Forehead 1 81.52 75.00 35.332 32.00 183.00 25.904 <0.001
2 74.10 67.00 36.289 26.00 175.00
3 64.43 67.00 29.949 19.00 137.00
Nose 1 86.38 61.00 80.367 3.00 276.00 26.146 <0.001
2 76.81 59.00 65.323 1.00 256.00
3 62.33 50.00 50.304 1.00 205.00
Cheek 1 51.64 48.00 29.666 15.00 124.00 17.429 <0.001
2 45.40 44.00 31.589 3.00 115.00
3 37.96 38.00 30.504 2.00 126.00
Eye area 1 52.06 49.00 29.405 11.00 131.00 22.519 <0.001
2 46.08 43.00 23.965 10.00 96.00
3 40.28 37.00 24.137 0.00 86.00
TEWL Forehead 1 17.94 17.90 6.339 10.00 38.00 27.714 <0.001
2 14.59 14.80 4.548 6.10 24.00
3 13.80 14.60 3.979 6.00 21.50
Cheek 1 20.18 18.50 7.711 10.50 37.00 36.286 <0.001
2 16.56 14.00 7.350 7.40 34.50
3 13.30 11.80 6.859 5.00 31.50
Eye area 1 19.46 18.90 4.876 10.80 31.50 27.524 <0.001
2 16.46 14.60 5.121 8.40 25.20
3 13.42 12.30 3.935 8.30 22.00
pH Forehead 1 5.92 5.80 0.426 5.15 6.83 40.095 <0.001
2 5.60 5.52 0.316 5.11 6.30
3 5.40 5.35 0.255 4.93 5.99
Nose 1 5.80 5.90 0.318 5.10 6.40 40.095 <0.001
2 5.54 5.55 0.306 4.94 6.20
3 5.39 5.40 0.268 4.77 5.83
Cheek 1 5.81 5.77 0.356 5.39 6.96 34.048 <0.001
2 5.51 5.46 0.270 5.00 5.91
3 5.26 5.20 0.245 4.90 5.78
Eye area 1 5.67 5.64 0.331 5.09 6.50 35.880 <0.001
2 5.50 5.52 0.238 5.02 5.97
3 5.25 5.24 0.242 4.83 5.68

TABLE 2.

Statistical analysis of the studied parameters according to the site before, during, and two weeks after the series of oxybrasion treatments with 10% gluconolactone.

Friedman's variance analysis
Measurement Mean value Median SD Min Max Statistics p‐Value
Hydration Forehead 1 51.35 52.63 10.021 32.30 70.00 33.904 <0.001
2 55.28 54.50 9.240 40.90 72.60
3 60.08 58.10 8.335 48.80 76.12
Nose 1 26.1 29.9 11.441 11.0 46.4 34.381 <0.001
2 35.93 37.30 10.346 14.40 50.00
3 43.07 42.37 13.262 16.50 67.60
Cheek 1 38.43 42.13 12.419 7.00 65.80 31.143 <0.001
2 46.35 48.40 9.457 29.60 62.70
3 52.88 53.80 11.152 31.70 69.00
Eye area 1 50.13 50.70 10.210 25.00 71.60 42.000 <0.001
2 56.78 56.60 11.768 27.01 73.10
3 64.05 69.70 12.753 39.68 80.00
Sebum Forehead 1 75.57 79.00 32.491 17.00 149.00 20.519 <0.001
2 67.10 66.00 30.666 20.00 140.00
3 56.81 57.00 27.491 5.00 120.00
Nose 1 86.62 63.00 69.770 7.00 246.00 18.317 <0.001
2 79.10 63.00 67.296 7.00 263.00
3 71.81 51.00 57.577 6.00 220.00
Cheek 1 49.46 42.00 33.486 3.00 135.00 21.133 <0.001
2 42.60 32.00 31.878 1.00 131.00
3 35.70 25.00 30.572 0.00 105.00
Eye area 1 54.76 57.00 26.653 9.00 100.00 23.301 <0.001
2 50.72 52.00 25.447 8.00 95.00
3 41.58 44.00 24.331 0.00 79.00
TEWL Forehead 1 17.72 17.20 5.447 10.60 37.00 24.747 <0.001
2 14.74 14.40 3.172 8.40 20.90
3 13.59 12.90 3.324 7.70 20.30
Cheek 1 21.29 19.50 8.485 11.70 52.00 33.238 <0.001
2 16.90 15.50 6.144 8.70 35.00
3 14.12 12.40 6.019 8.30 36.00
Eye area 1 19.14 19.40 4.985 8.20 30.00 26.000 <0.001
2 16.90 14.90 4.485 11.00 26.00
3 15.10 14.80 4.206 8.00 23.00
pH Forehead 1 5.84 5.85 0.327 5.31 6.53 34.667 <0.001
2 5.65 5.69 0.249 5.27 6.15
3 5.38 5.37 0.273 5.00 5.90
Nose 1 5.63 5.65 0.299 5.15 6.30 34.667 <0.001
2 5.40 5.34 0.249 4.92 5.97
3 5.25 5.21 0.232 5.00 5.90
Cheek 1 5.70 5.74 0.328 5.11 6.40 30.902 <0.001
2 5.47 5.54 0.301 4.95 5.91
3 5.22 5.16 0.254 4.66 5.70
Eye area 1 5.75 5.72 0.248 5.30 6.50 38.095 <0.001
2 5.51 5.59 0.211 5.10 5.92
3 5.30 5.32 0.272 4.90 5.77

3.6. Photo documentation

In photos taken with the Fotomedicus system (Elfo) (Figures 6, 7, 8, 9) under the same lighting conditions, the improvement of the skin condition can be manifested as the following:

  1. reduction of inflammatory changes,

  2. unification of skin texture,

  3. reduction of acne lesions,

  4. reduction of fine wrinkles.

FIGURE 6.

FIGURE 6

Forty‐two years old female probant before (A) and 2 weeks after (B) the treatment series.

FIGURE 7.

FIGURE 7

Forty‐two years old female probant before and 2 weeks after 10% gluconolactone with microneedling (A and B) and before and after 10% gluconolactone with oxybrasion (C and D).

FIGURE 8.

FIGURE 8

Thirty‐nine years old female probant before (A) and 2 weeks after (B) the treatment series.

FIGURE 9.

FIGURE 9

Thirty‐nine years old female probant before and 2 weeks after 10% gluconolactone with microneedling (A and B) and before and after 10% gluconolactone with oxybrasion (C and D).

4. DISCUSSION

In the available publications, there are no studies on the use of chemical peeling of gluconolactone in combination therapies with oxygen microdermabrasion or skin micropuncture. Several authors describe the combination of diamond or aluminium microdermabrasion with lactobionic acid, lactic acid and their mixtures, as well as chemical peels with micro‐needle mesotherapy. 2 , 4 The properties of each of these treatments individually are also well‐known.

In our study, measurements with the Corneometer CM 825 probe, Courage (Courage + Khazaka electronic GmbH, Cologne, Germany) showed a significant increase in skin hydration following application of both techniques: gluconolactone in combination with oxybrasion and with superficial microneedling of the skin with the Derma Skin Pen. Previous in‐house studies of water‐oxygen microdermabrasion 5 and a series of treatments using two concentrations of gluconolactone 9 also reported an increase in hydration of the superficial layers of the skin. Gluconolactone has the property of “attracting” water molecules, which is due to the presence of as many as four hydroxyl groups in its structure: this substance acts as a humectant. Furthermore, gluconolactone is converted to gluconic acid during the hydrolysis reaction, increasing therefore the number of hydroxyl groups and its ability to bind to water. 19 , 20 , 21

A series of original treatments that combined gluconolactone with oxybrasion and skin microneedling resulted in a decrease in sebum levels at all measurement sites, which may be related to the strengthening of the epidermal barrier by gluconolactone. It also reduced inflammatory lesions and contributed to the alleviation of acne lesions. Gluconolactone strengthens the epidermal barrier, reduces inflammatory lesions and produces antiacne effects. Hunt et al. showed that a lotion with 14% gluconolactone compared to 5% benzoyl peroxide (commonly used to treat acne) shows greater efficacy and does not cause irritation. 11 , 22 , 23 Both microneedle mesotherapy and hydrogen peroxide microdermabrasion promote the penetration of the active ingredient. Additionally, during the oxybrasion treatment, an oxygen environment is produced on the epidermal surface, which can contribute to a decrease in C. acnes, that is, anaerobic bacteria. 5 , 7 , 24 , 25 , 26

In a previous self‐study, statistical analysis showed that oxygen microdermabrasion alone did not significantly affect the TEWL parameter. 5 In the current study, a significantly statistical decrease in transepidermal water loss was observed after the completion of the treatment series compared to measurements taken before the first treatment on both the microdermabrasion and microneedling sides. Oxybrasion can enhance the properties of the active ingredient. Gluconolactone may contribute to reducing TEWL. It is important to note that gluconolactone is produced from glucose, which forms a delicate film on the surface of the skin, sealing the hydrolipid barrier and preventing the evaporation of water from the epidermis. 19 , 20 , 25 , 26 Berardesca et al. conducted a study in which participants applied four formulations containing 8% glycolic acid, 8% tartaric acid, 8% gluconolactone, and 8% lactic acid, respectively, to the skin for four weeks, twice daily. In the fourth week, 5% SLS was applied to the studied areas under a 6‐h occlusion. The study evaluated the effect of hydroxy acids on the skin barrier and showed that the sites where gluconolactone was applied had the lowest TEWL values. 27 Skin microneedling also has an effect on the TEWL parameter. Robati et al. showed that dermapen treatment was effective in reducing transepidermal water loss. 28

In the pH assessment in our study, a significant decrease in this parameter was observed during and after the study. In this case, both treatments were also found to contribute to lowering of the pH of the skin, while no statistically significant differences were identified between the use of gluconolactone in combination with oxybrasion and micro‐needle mesotherapy. Researchers emphasize that in the treatment of inflammatory dermatoses, it is essential to create an acidic environment on the skin surface. 29

Photographic documentation comparing skin condition before and after treatments showed a significant improvement in skin texture, smoothing and brightening. This may be related to improved hydration and strengthening of the hydrolipid barrier.

5. CONCLUSIONS

Combination treatments based on a series of procedures with 10% gluconolactone and oxybrasion of the same peel with micro‐needle mesotherapy showed:

  1. normalization of the lipid coat of the skin,

  2. reduction of transepidermal water loss,

  3. lowering of pH,

  4. increase in hydration of the stratum corneum.

Both treatments show high efficacy; however, no significant differences were observed between the techniques.

FUNDING INFORMATION

Medical University of Lodz, Grant Number: 503/3‐066‐01/503‐31‐001‐19‐00.

CONFLICT OF INTEREST STATEMENT

The authors report no declaration of interest. The authors themselves are responsible for content and writing of the paper.

ACKNOWLEDGMENTS

The study was supported by statutory research activity number: 503/3‐ 066‐01/503‐31‐001‐19‐00.

Jarząbek‐Perz S, Dziedzic M, Kołodziejczak A, Rotsztejn H. Split‐face evaluation: Gluconolactone plus oxybrasion versus gluconolactone plus microneedling. The effects on skin parameters. Skin Res Technol. 2023;29:e13353. 10.1111/srt.13353

DATA AVAILABILITY STATEMENT

All data generated or analyzed as part of this study are included in this article. Further inquiries can be directed to the corresponding author.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

All data generated or analyzed as part of this study are included in this article. Further inquiries can be directed to the corresponding author.


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