A cosmetic treatment based on the secretion of Cryptomphalus aspersa 40% improves the clinical results after the use of nonablative fractional laser in skin aging

Abstract Introduction The main purpose of this study was to evaluate whether the application of a cosmetic treatment based on the secretion of Cryptomphalus aspersa (SCA) enhances the clinical results, tolerance, and skin regeneration after nonablative laser treatment in patients with moderate photoaging. Methods Randomized, double‐blind, split‐face trial in 20 patients with moderate aging. Two sessions with fractional nonablative laser were performed, and the cosmetic treatments (SCA 40% on one hemiface and vehicle on the other) were applied immediately after laser session and daily during the study (28 days). Tewameter, Cutometer, Visioscan, VisioFace, photography, dermoscopy, and clinical evaluation were assessed. Side effects were also evaluated. Results A significant decrease in the density of microcolumns (25%, 71%, 32%, and 61% less density, respectively, at T3 P = 0.008, T7 P = 0.002, T22 P < 0.001, and T24 P < 0.001) was observed on the side treated with SCA compared to the vehicle‐treated side. Cutaneous elasticity, area of wrinkles, and hydration on the SCA‐treated side also showed a significant improvement compared to the vehicle‐treated side. Both the researcher and patients observed a significant improvement on the side treated with SCA compared to the vehicle‐treated side. Significantly fewer side effects (erythema, burning, and dryness) were also detected. Conclusion A cosmetic product with SCA 40% applied immediately after laser and for a period thereafter enhances and accelerates repair of damage produced by the laser and significantly reduces related adverse effects. In addition, SCA treatment could improve clinical results. In conclusion, we suggest that SCA enhances the effectiveness of laser in the treatment of cutaneous aging.


| BACKG ROU N D
Skin aging is a physiological process determined by endogenous mechanisms and external environmental aggression. 1 Exposure to the sun, pollution, and tobacco triggers molecular processes that damage the skin structure, leading to an aged skin appearance.
Other, less well-studied factors (temperature, lack of sleep, nutrition, and stress) also promote cutaneous aging. 2 The subsequent activation of nuclear factor-κB (NF-κB) and factor activating protein-1 (AP-1) through different mechanisms induces the expression of matrix metalloproteinases, accelerating matrix degradation. [3][4][5][6] Skin aging treatments include different approaches. Among them, nonablative fractional laser technology consists in applying the laser energy that penetrates the skin forming small microcolumns (MTZs: microscopic thermal zones) leaving part of the skin intact where heat accumulates and biological effects occur: increased vascularity, greater supply of nutrients, and stimulation of the synthesis of collagen. The undamaged skin acts as a reservoir of that heat and contributes to create new skin improving the aesthetic appearance of the skin. [7][8][9] Dermal activation induces new collagen with consequent clinical improvement. 10,11 With the use of nonablative fractional laser, the recovery time is faster and side effects are fewer when compared to ablative fractional laser. 8 In addition, nonablative fractional lasers are successful in increasing the penetration of cosmetics and drugs applied topically after the laser session (laser assisted drug delivery). 8,[12][13][14][15][16] In the present study, we applied a cosmetic product containing SCA 40% immediately after laser treatment. SCA 40% is a cosmetic ingredient obtained from gastropods of the family Cryptomphalus aspersa. The analytical profile of the secretion indicates a richness of proteins of low molecular weight, similar to the fibroblast growth factor; antioxidant enzymes; and glycosaminoglycans. 17,18 Through numerous studies, SCA demonstrated its ability to induce cutaneous regeneration and antioxidant efficacy through superoxide dismutase and glutathione transferase activity. 19,20 Several in vitro and clinical studies have shown that SCA stimulates the proliferation and migration of fibroblasts and keratinocytes accelerating the process of wound healing. [21][22][23][24]

| AIMS
The main objective of this study was to assess the efficacy of the cosmetic product under study (SCA 40%) in inducing faster skin recovery after performing a nonablative fractional laser treatment in patients with moderate photoaging. As secondary objectives, we studied the synergistic effectiveness in improving the laser procedure outcome and the subjective evaluation of photoaging improvement perceived by patients and the investigator.

| PATIENTS/ME THODS
This was a prospective, randomized, double-blind, split-face study where SCA 40% was applied to one side of the face versus vehicle on the other in 20 patients. The active treatment (SCA) or the vehicle was randomly assessed to be applied in the right hemiface (RH) or the left hemiface (LH), the patient acting as his/her own control.
Patients with moderate facial skin aging were recruited (minimum assessment of 3 on the scale of Rao-Goldman), and featured the following inclusion criteria: • Aged 45-65 years.
• Absence of other skin treatments during the last 3 months The study followed the tenants of the Declaration of Helsinki.

| Treatment regimen
The active formula included SCA 40%. Treatments were performed with nonablative fractional laser, and two laser sessions were performed, the first at T0 and the second at T21. A 1540-nm Erb-glass laser from the ICON platform of Palomar Technologies (Cynosure, Madrid, Spain) was used at 50 mj of energy and pulse duration of 15 ms. Three passes were made on the patient's face in each of the sessions. The product was applied immediately after the laser treatment session and during the subsequent 28-day study period.
The product was applied every 12 hours for the first 7 days after performing the laser session and then every 24 hours until the next laser session. After the second session, the product was applied again every 12 hours during the remaining 7 days of the study. The patients also applied topical photoprotection (Heliocare 360 Mineral Tolerance Fluid) in the morning from T8 to T21. Eight visits were performed: T0 (first laser session), T1d (24h), T3d (72h), T7d, T21d (second laser session), T22d (24h), T24d (72h), and T28d.

| Clinical assessment
At all visits, clinical assessment, photography, and transepidermal water loss (TEWL) as hydration measurement were carried out. The assessment of skin elasticity and firmness (Cutometer) and the quantitative assessment of wrinkles and skin texture were performed at T0 and T28.

| Statistical study
For the efficacy variables of ordinal nature, a nonparametric Wilcoxon test was performed. For the quantitative variables, mixed linear models (MLM) and generalized estimation equations (GEE) were used. As descriptors, the most usual values of centralization, dispersion, and position were used in all cases: mean, standard deviation, and median. A difference between the hemifaces was considered statistically significant at P ≤ 0.05. R software was used to perform the statistical calculations.

| RE SULTS
We included 20 subject volunteers, and there were not dropouts or exclusions. showed an 80% greater improvement on the active-treated side vs

F I G U R E 2 Evolution of microcolumn density with the active (left) and vehicle (right) treatments in Patient 15
F I G U R E 3 Graph with the summary of evolution of transepidermal water loss (TEWL) on the side treated with the active (A) and vehicle (V). A peak of increase was observed at T0 and also at T22 immediately after the second laser session. T, time the vehicle-treated side (P = 0.032). PGA at T7 and T21 showed a 90% and 70% difference, respectively, in the improvement assessment in favor of the active (P = 0.032 and P = 0.042) (Figure 4).

| D ISCUSS I ON
Fractional laser induces a controlled damage consisting of microcolumn generation in the skin. A significantly lower microcolumn density was quickly detected at the SCA-treated side, improving recovery time when compared to vehicle. In addition, we suggest that cutaneous regeneration could be accelerated with the use of SCA, as we observed significantly lower microcolumn density just after 24 hours (T22) of the second procedure, faster than with the first laser when significant improvement was after 72 hours (T3).
The TEWL levels reflect the state of the barrier function.
Although nonablative laser did not produce direct damage to the stratum corneum, significant increases in TEWL were detected in Regarding PGA and IGA, a week after the laser treatment, both the researcher and patients found a significantly greater improvement on the side treated with the active, suggesting that the application of SCA improves global perception of improvement. All results obtained are coherent, with the correlation between improvement in the recovery of microcolumns, reduction in TEWL, and reduction in adverse effects such as erythema, burning, and tightness.
In conclusion, the application of a cosmetic product formulated with SCA 40% immediately after laser treatment and during the following days accelerates recovery from the damage produced by the laser and significantly reduces associated adverse effects. In addition, it is suggested that SCA enhances the effectiveness of the laser in the treatment of aging in terms of elasticity and reduction in wrinkle area.

CO N FLI C T O F I NTE R E S T
Dra Truchuelo is scientific adviser to Cantabria Labs.