Whitening and moisturizing enhancing effects of three‐dimensional human adipose‐derived mesenchymal stem cell‐conditioned medium‐containing cream

High‐functional cosmetic products combined with the concept of “treatment” cosmetics are being introduced to the market. Cosmetic products containing a skin‐derived microbiome, a three‐dimensional (3D) stem cell culture medium, and low‐molecular‐weight collagen are being introduced, and these products are leading the cosmeceutical market. We aimed to confirm the potential of a 3D stem cell culture medium‐containing cream as a skin‐whitening and moisturizing product.


| INTRODUC TI ON
Many people dream of having a brighter skin tone, and an increasing number of people are taking care of their skin and gaining interest in whitening cosmetics and procedures.The disruption of the skin barrier in dry skin engenders skin issues, including eczema and psoriasis, and can also result in a dull skin tone.Moisturization is necessary for skin brightening, and sufficient hydration is essential for maintaining healthy skin.Exposure to and damage from ultraviolet (UV) radiation can make the skin dry and wrinkled, thereby roughening its texture.This damage happens because the epidermis, which acts as a barrier that prevents the loss of water from the body and maintains the moisture content, is damaged by UV rays, thereby decreasing skin moisture. 1,2Especially during winter, the metabolism of the skin is reduced and sebaceous gland secretion is decreased, which lead to tightened and flaky skin.Therefore, during winter, interest in cosmetics that provide improved whitening and moisturizing effects increases.To sustain the moisturizing hyaluronic acid (HA) level in the stratum corneum of the skin, HA synthase (HAS) activity must be continuously maintained. 3lanocytes originating from the neural crest produce melanin and are essential for protecting the skin from UV rays.Skin pigmentation is a major physiological defense mechanism that counteracts the harmful effects of UV rays, such as DNA damage to the skin cells caused by melanin biosynthesis. 4Melanin, synthesized in melanocytes via melanogenesis, is stored in melanosomes and eventually migrates to keratinocytes and is distributed throughout the epidermis.Melanogenesis involves a series of enzymatic reactions that convert tyrosine to melanin. 5 Tyrosinase (TYR), TYR-related protein (TRP)-1, and TRP-2 are involved in the process.TYR is an essential and rate-limiting enzyme that catalyzes the conversion of l-tyrosine to l-dihydroxyphenylalanine (l-DOPA), the precursor of melanin. 6e expression of TYR is regulated by microphthalmia-associated transcription factor, which controls skin pigmentation and the differentiation, proliferation, and survival of melanocytes. 7em cells are categorized into two types according to their cytological origin: embryonic and adult stem cells.Adipose-derived mesenchymal stem cells (ADMSCs), which are present in the adipose tissue, are a population of totipotent mesenchymal stem cells that exhibit characteristics similar to bone marrow-derived mesenchymal stem cells.Human ADMSC-conditioned media (ADMSC-CM) contains various growth factors and cytokines secreted during adiposederived stem cell culturing, 8 and its contents can be quantified, thereby facilitating its use as a composite for cosmetics and various other products.Existing studies on conditioned media have mostly concentrated on two-dimensional (2D) monolayer culture and do not reflect the in vivo environment; however, there have been studies on three-dimensional (3D) culture in an environment akin to in vivo. 9In 3D cell culture, scaffold-dependent methods that make use of porous polymers or natural polymer hydrogels, such as collagen, agarose, and gelatin, are widely employed.The selection of the scaffold is extremely important for cellular proliferation and maintenance of cell properties. 10 has previously been reported that the various growth factors present in human adipose-derived stem cell culture media are effective in whitening and wound healing. 11These growth factors (GFs) include fibroblast GF, vascular endothelial GF, platelet-derived GF, insulin-like GF, keratinocyte GF, hepatocyte GF, granulocyte colony-stimulating factor, and granulocytemacrophage colony-stimulating factor.These are implicated in angiogenesis alleviation, wound healing, skin whitening, and damaged cell regeneration. 10,12,13A previous study demonstrated the inhibitory effect of adipose-derived stem cell protein on melanin synthesis and reported the important role of the regulation of GFs, such as transforming growth factor-β1, in it. 14During melanogenesis, the main enzyme TYR produces an intermediate product called l-DOPA using l-tyrosine as a substrate with the help of TYR-related protein-1 (TYRP1) and TYRP2.Following oxidation to dopaquinone, pheomelanin and eumelanin are eventually produced via additional mechanisms. 15erefore, this study investigated the effect of 3D ADMSC-CM on the whitening and moisturizing effects of a cosmetic cream via human trials and aimed to confirm the potential of 3D ADMSC-CM as a novel raw material for biocosmetic use.

| Cell lines and cell culture
The cell lines used in this study were human dermal-derived fibroblasts (HDFs) and human ADMSCs of men aged <20 years, which were purchased from CEFO Co.
2. Melanocytes were cultivated in a melanocyte-specific culture medium (Bullet Kit, Lonza) in an incubator at 37°C, 5% CO 2 , and ≥95% relative humidity, and the medium was replaced once every 2-3 days.
3. 3D adipose stem cell culture.Biodegradable synthetic biogel Kolliphor®P 407 (BASF) was dissolved in tertiary distilled water at a concentration of 10% to prepare the gel, applied at 250 μL/cm 2 on Transwell (Corning), and allowed to solidify for 90 min at 37°C to create the 3D cell culture environment.Subsequently, human ADMSCs cultured in a dish using the original culture method were seeded on the preformed biodegradable synthetic biogel, and the cells were incubated in a CO 2 incubator at 37°C.The culture medium was replaced 1 day after the stabilization of the cells.
4. Securing a conditioned medium for human ADMSCs.3D ADMSC-CM was obtained as per the method described by Kim et al. 16,17

| 3D ADMSC-CM cream preparation
The water phase was added to the main beaker and heated by stirring.A liquid crystal emulsifier was added to the heated water phase at 80°C and hydrated using a homogenizer (80°C, 6000 rpm, 10 min).
The oil phase was added to a separate dissolution tank and heated to 80°C.The oil phase was then added to the main beaker, mixed with the water phase, and emulsified using a homogenizer (75°C, 6000 rpm, 5 min).The main beaker containing the mixed water and oil phases was cooled to 45°C, and the liquid emulsifier capsule was encapsulated by stirring in a separate beaker.The capsule was added to the water and oil phases in the main beaker and stirred using a homogenizer (45°C, 6000 rpm, 3 min), and the main beaker was cooled to 33°C.3D ADMSC-CM was included in a 1% cream formulation.

| TYR activity inhibition test
The reaction solution was reacted in a 96-well plate at 37°C for 15 min, and the absorbance was read at 475 nm using a microplate reader (Molecular Device).
where A: proceed by adding buffer instead of sample; A′: proceed without TYR under condition A; B: proceed by adding sample; B′: proceed without TYR under condition B.

| Melanin inhibition test
Melanocytes were seeded in a 12-well plate at a concentration of 1 × 10 5 cells/well and cultured in an incubator at 5% CO 2 and 37°C for 24 h.After treating the adhered cells with control, 2 mM arbutin (a whitening agent), 2D ADMSC-CM, or 3D ADMSC-CM, they were recovered after 48 h.Next, 3 N NaOH was added and reacted in an incubator at 37°C for 30 min, and the absorbance was read at 405 nm using a microplate reader (Molecular Device).

| Confirmation of HA expression
To determine the performance of the SC-CM in HA expression, HDFs were seeded in a well plate (Corning) at 6 × 10 4 /cm 2 , and the culture medium was replaced after 24 h.The media for the control group were replaced with fibroblast culture media, and the test group was treated with 50% SC-CM for 24 h using the 2D and 3D conditioned media.Later, the expression of HA was determined using the enzyme-linked immunosorbent assay (ELISA) kit (Echelon Biosciences).The test was performed according to the manufacturer's instructions.

| Human trial
Human trial was conducted to confirm the effectiveness of 3D ADMSC-CM cream, and the trial was approved by the research ethics committee.

| Test participants
This study included women aged 20-60 years and was intended to verify the efficacy of the test product.The skin antioxidant effect of ADMSC-CM was measured before use as well as 2 and 4 weeks after use on 22 participants.Skin tone, freckles, and radiance were assessed before as well as 2 and 4 weeks after use on 20 participants.
The moisturizing effect of ADMSCs was evaluated before and 5 min after exposure to cold or dry weather conditions on 24 participants with dry skin.

| Skin tone evaluation
To evaluate the skin tone, participant faces were photographed before and after the experiment using Visia-CR (Canfield Imaging Systems) and the Standard 2 mode of the image was analyzed using Image-Pro® Plus.After designating a specific area in the image, the skin tone was evaluated by representing the skin brightness of the area as the L* value and skin redness as the a* value.A higher L* value indicated an improvement in the skin tone, and a lower a* value signified a soothing effect on the skin.

| Skin radiance evaluation
Skin radiance was assessed by photographing the faces of the participants before and after the experiment using Visia-CR, and the parallel mode of the image was analyzed using Image-Pro® Plus.After designating a specific area in the image, the skin radiance effect was evaluated based on the intensity value indicating the brightness of the skin in that area.Higher intensity values represented an enhanced skin radiance effect.

| Skin freckle evaluation
To evaluate skin freckles, the Antera 3D CS (Miravex Ltd.), a 3D skin imaging device, was used to photograph the same pigmented area on the left cheek before and after the experiment.The image was converted to the melanin-hyperconcentration mode, and the skin freckle area (mm 2 ) was analyzed after designating an analysis area of 44.8 mm in a circular form.A decrease in the area values signified alleviation of skin freckles.

| Moisturizing effect under extreme cold and dry weather conditions
The test area of the participants was photographed twice.The participants washed their forearms using a foam cleanser and waited for 30 min under constant temperature and humidity conditions (20-24°C, 40%-60% relative humidity) before proceeding with the experiment.
1. Extreme cold weather conditions.For this experiment, the forearm area of the participants was divided into a region 3 × 3 cm 2 in width and length at a distance of 5-10 cm from the wrist.
The product was applied at a rate of 2-L/cm 2 on the test area, patted for sufficient absorption, and subjected to cold weather conditions for 5 min (5-10°C).A corneometer was used to measure the skin moisture content of the test area.
2. Dry weather conditions.For this experiment, the forearm area of the participant was divided into a region 3 × 3 cm 2 in width and length at a distance of 5-10 cm from the wrist.The product was applied at a rate of 2-L/cm 2 on the test area, patted for sufficient absorption, and subjected to dry weather conditions for 1 h (22 ± 2°C, <35% relative humidity).A corneometer was used to measure the skin moisture content in the test area.
The skin moisture content before and after the experiment was measured thrice using Corneometer CM825 (Courage and Khazaka), and the average of the measured values was obtained.
The skin moisture content was measured before and after exposure to cold and dry weather conditions, and the rate of increase in the skin moisture content was obtained using the following formula:

| Statistical analysis
For evaluating the antioxidant and moisturizing effects, IBM SPSS Statistics version 26.0 was used, and significance was set to p < 0.05.
To determine the significance of the measured values for skin tone, radiance, and freckles before and after the experiment, SPSS 19.0 was used, and significance was confirmed when the significance probability was p < 0.05.

| Confirming the inhibitory effect of TYR
TYR is present in the basal layer of the epidermis and promotes melanogenesis by oxidizing TYR in melanocytes.Its inhibition is crucial for skin whitening and prevention of skin aging.Arbutin was used as the positive control of the TYR inhibition test of 3D ADMSC-CM (Figure 1).TYR inhibition assay was performed in the 3D ADMSC-CM.
Arbutin, 2D ADMSC-CM, and 3D ADMSC-CM were mixed with 100 U/mL of mushroom TYR in a potassium PBS (pH 6.5).l-DOPA substrate (1 mM) was added to the reaction mixture and incubated for 15 min.The change in absorbance was measured at 475 nm using a microplate reader.All replicates (n = 3) are displayed in the results

graph.
The inhibitions of TYR were approximately 44% (2D ADMSC-CM) and 24% (3D ADMSC-CM) compared with those during arbutin treatment, the positive control, thereby confirming the inhibitory effect of ADMSC-CM against TYR.Hence, both 2D and 3D ADMSC-CM were confirmed to have significant effects compared with the positive control.Therefore, SC-CM prepared using 3D ADMSC was established to be beneficial in inhibiting TYR activity.

Rate of increase of skin moisture content(%)
= ([measured value after experiment − measured value before experiment]∕ [measured value before experiment]) × 100

| Melanin contents
Melanogenesis occurs in the ribosomes via TYR biosynthesis.
Melanin synthesis uses tyrosine, an amino acid, as a substrate and is metabolized to DOPA and dopaquinone by TYR.After the formation of dopaquinone, either pheomelanin is formed, which changes from a reddish-brown color to yellow, or eumelanin is formed, which changes from a dark brown color to brown. 18lanocytes were incubated with 2 mM arbutin, 2D ADMSC-CM, and 3D ADMSC-CM for 48 h, after which all the cells were harvested with 3N NaOH and incubated for 30 min.The absorbance was measured at 450 nm using a microplate reader.All replicates (n = 3) are displayed in the results graph.(A) Graph, (B) image.
Melanocytes were used to measure the inhibitory effect of 3D ADMSC-CM on melanogenesis, and 2 mM arbutin was used as the positive control (Figure 2).The inhibition of melanogenesis was found to have been reduced by approximately 40% in the control group compared with the positive control group (2 mM arbutin) and inhibited by approximately 23% and 33% in the 2D ADMSC-CM and 3D ADMSC-CM groups, respectively.Hence, 3D ADMSC-CM was confirmed to exhibit a significant level of melanogenesis inhibitory activity compared with the positive control, thereby confirming its superior melanogenesis activity.

| HA expression effect
HA is used as a moisturizer in various cosmetics as it contains a large amount of water. 19HAS2 is an enzyme that produces HA in keratinocytes.HAS2 is present in the basal layer of the epidermis, but progressive skin aging due to UV exposure and defects in the moisture barrier of the skin reduce HAS gene expression, thereby decreasing the amount of HA. 20 Therefore, in this study, HDFs with increased expression of the HAS2 gene were treated with 3D ADMSC-CM.Subsequently, ELISA was used to determine the enzyme-binding ability and measure HA expression (Figure 3).HDFs were treated with 50% 2D and 3D ADMSC-CM for 24 h.ELISA was performed using the harvested 2D and 3D ADMSC-CM.
Values represent the mean ± standard deviation of three independent measurements.*Means compared with control.
ELISA revealed an increase in the HA expression in the 3D ADMSC-CM group compared with the 2D ADMSC-CM group after 24 h of treatment.Therefore, the facilitative role of 3D ADMSC-CM in increasing the HA levels by augmenting the HAS function was confirmed, which is expected to enhance moisturization when used as a cosmetic ingredient.The skin moisturizing efficacy of human dermal stem/progenitor cell-derived conditioned medium (hDSPC-CM) has also been reported in human keratinocytes. 21

| Human trials
Exposure to UV radiation is the primary reason for photoaging, which results in symptoms such as reduced skin moisture, decreased elasticity, wrinkling, and pigmentation, including erythema. 22When skin moisture decreases, the physiological function of the skin is compromised, thereby increasing wrinkles and accelerating skin aging.Hence, supplying sufficient moisture to the skin and preventing its evaporation are necessary to maintain healthy skin.
No adverse skin reactions have been reported in study participants because of the use of 3D ADMSC-CM cream, 16 which is consistent with the observations of our study.

| Evaluation of the antioxidant effect on skin
Vitamin A is commonly used as an antioxidant cosmetic raw material, and other natural and synthetic antioxidant ingredients have F I G U R E 1 Inhibitory effect of three-dimensional adipocyte-derived mesenchymal stem cell-conditioned media (3D ADMSC-CM) on tyrosinase (TYR) activity.
been developed and used in numerous cosmetics.By applying a protein with antioxidant activity to 3D ADMSC-CM in a creamtype cosmetic formulation, the possibility of using it as a cosmetic ingredient with antioxidant activity was determined.
In this study, to evaluate the antioxidant effect of 3D ADMSC-CM cream on the skin, efficacy evaluation was conducted before use and 4 weeks after use, and the antioxidant property was determined by measuring the CP levels in the facial area (Figure 4).Dead skin cells were collected via single-tape stripping from specific skin areas before use and 4 weeks after use.Dead skin cells were reacted in 50 mL of a 20 mM fluorescein-5-thiosemicarbazide solution for 1 h and then washed thrice with PBS.Paired t-test was performed to determine statistical significance (*p < 0.001).
The measured CP value of the facial area decreased to a statistically significant level (*p < 0.001) after 4 weeks of use compared with that before use, and a reduction rate of 41.393% was observed (Figure 4A).The decrease in CP values 4 weeks after use compared with those before use was confirmed via imaging (Figure 4B).Thus, 3D ADMSC-CM cream exhibited an antioxidant effect on the skin after 4 weeks of use.
Antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxide, inactivate or remove reactive oxygen species associated with membrane lipid peroxidative damage, inactivate sulfhydryl-containing enzymes, and cross-link integral proteins. 23According to a previous report, treatment with paraquat, an electron transport system disruptor, during in vitro culturing of mouse embryonic stem cells did not alter the activity of alkaline phosphatase, a marker of undifferentiated stem cells.However, the treatment reduced cell viability and doubled reactive oxygen species generation.Furthermore, when treated with ascorbic acid, the viability of the embryonic stem cells was restored to a value similar to that of the control group.The skin of the participant was photographed before and after using the test product.The entire face was compared before use as well as 2 and 4 weeks after the use of the test product.
A statistically significant increase in the skin tone (p < 0.05) was observed 2 and 4 weeks after using 3D ADMSC-CM cream compared with the skin tone before use.Skin radiance exhibited a statistically significant increase (p < 0.05) 4 weeks after use compared with that before use of the cream.Thus, 3D ADMSC-CM cream application was confirmed to help improve skin tone and radiance.
The GFs present in the stem cell-conditioned medium exhibit skinwhitening effects and are, thus, used in skin-brightening cosmetics and under-eye dark-circle reduction products. 25

| Skin freckle evaluation
Freckles and pigmentation are caused by melanogenesis in melanocytes, increased melanogenesis because of certain factors, and the large amount of melanin produced, transferred to keratinocytes, and accumulated in the epidermal layer.Melanin pigmentation is not only recognized as a cosmetic problem but also as a pathological problem.
The effects of 3D ADMSC-CM cream application on freckle improvement are shown in Figure 6.
The entire face was compared before use and after 2 and 4 weeks of use.Friedman test was conducted to determine statistical significance (*p < 0.025).A significant (p < 0.025) decrease was observed in skin freckles after 2 and 4 weeks of using 3D ADMSC-CM compared with that before use.For healthy and elastic skin, an appropriate amount of skin moisture must be maintained, and a skin barrier that can minimize moisture loss even under dry conditions must be constituted.
The moisture content of the skin varies greatly according to the changing seasons.To measure the skin moisturizing effect of 3D ADMSC-CM cream according to temperature, the effect was evaluated under cold (5-10°C) and dry (22 ± 2°C, <35%) weather conditions (Figure 7).The measured values of skin moisture under cold F I G U R E 5 Analysis of skin tone and radiance after the application of the cream containing three-dimensional adipocyte-derived mesenchymal stem cell-conditioned medium (3D ADMSC-CM).Shows the results of the cream on skin tone (A) and skin radiance (B).

F I G U R E 6
Improvement in skin freckles after the application of the cream containing three-dimensional adipocytederived mesenchymal stem cellconditioned medium (3D ADMSC-CM).The results of freckles 2 weeks, 4 weeks were shown in graphs (A) and images (B).
weather conditions are shown in Figure 7A, and those under dry weather conditions are shown in Figure 7B.
The moisturizing effect of 3D ADMSC-CM cream was studied by categorizing the weather condition into cold weather (5-10°C) and dry weather (22 ± 2°C, <35%).Cold weather moisturizing was analyzed before and after 5 min of use, whereas dry weather moisturizing was analyzed before and after 1 h of use.The paired t-test was performed to determine statistical significance (*p < 0.001).
Following the application of 3D ADMSC-CM cream and 5 min of exposure to cold weather conditions, the measured value of skin moisture in the area where the cream was applied exhibited an increase of 93.60% (p < 0.001) and that of the unapplied area was −3.978% (p < 0.001).Following the application of the cream and 1 h of exposure to dry weather conditions, the measured value of skin moisture in the area where the cream was applied showed an increase of 99.070% (p < 0.001) and that of the unapplied area was −5.413% (p < 0.001).

| CON CLUS IONS
ADMSC-CM comprises various GFs and cytokines and can, therefore, be applied as a cosmetic raw material for skin whitening and regeneration as well as wrinkle improvement.This study confirmed the whitening and moisturization-enhancing effects of 3D ADMSC-CM as a cosmetic raw material via cytobiological experiments and clinical efficacy studies.First, the effects were studied via cytobiological experiments.The TYR and melanogenesis inhibitory activities of 3D ADMSC-CM were evaluated.The results demonstrated approximately 24% reduction in the inhibitory effect on TYR activity and approximately 33% reduction in the inhibitory effect on melanogenesis, thereby confirming the whitening effect of 3D ADMSC-CM.
The moisturizing effect of 3D ADMSC-CM was confirmed by its ability to enhance HA generation by increasing HA synthase, thereby increasing skin moisture.
The evaluation of the antioxidant effect of 3D ADMSC-CM cream showed that the measured CP value decreased 4 weeks after use compared with that before use, with a 41.393% reduction rate (p < 0.001), and this difference was statistically significant.In the evaluation of skin tone, compared with before applying the cream, skin tone and radiance increased significantly 2 and 4 weeks after use (p < 0.05) and skin radiance increased significantly after 4 weeks of use compared with that before use (p < 0.05).The improvement in skin freckles because of the use of the cream was significant after 2 and 4 weeks of use compared with that before use (p < 0.025).The moisturizing effect of the cream was measured in cold and dry weather conditions.
The measured value of moisturization during cold weather conditions showed an increase of 93.601% (p < 0.001) in the area where the cream was applied and that during dry weather conditions showed an increase of 99.070% (p < 0.001) in the application area.
The skin-whitening and moisturization-enhancing effects of 3D ADMSC-CM were confirmed via cytobiological tests, and clinical efficacy tests revealed that it enhanced skin whitening and moisturization.Accordingly, 3D ADMSC-CM cream can be used in the skin care and cosmetic industries as a biocosmetic.
To date, studies have been conducted on the potential of 3D ADMSC-CM for skin improvement via in vitro and in vivo experiments.Apart from efficacy in skin improvement, the percutaneous absorption rate also needs to be improved.Hence, more active research on the skin improvement mechanisms is warranted.We expect that such studies will be able to pioneer the development and bring to light the potential of 3D ADMSC-CM in the biocosmetic industry.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.

E TH I C S S TATEM ENT
The human trial was conducted to confirm the effectiveness of the 3D ADMSC-CM cream and was approved by the research ethics committee (IRB-200828T001, IRB-200908T001, P2008-1382).

CO N S ENT FO R PA RTI CI PATI O N
Written and informed consent was taken from all participants of the study.

D
-Squame Disks (Cuderm) were applied to the test (facial) area of the participants to collect dead skin cells via tape stripping once before use and 4 weeks after use.For fluorescent staining, 0.1 M MES-Na buffer (pH 5.5) was dissolved in fluorescein-5-thiosemicarbazide (FTZ; #F121, Invitrogen) buffer.The dead-skin-cell samples were placed in 50 mL of prepared 20 μΜ FTZ solution for 1 h and then washed thrice with 10 mL of phosphate-buffered saline (PBS).Carbonylated proteins (CPs) in the dead skin samples fluoresced.For imaging and analysis, each sample was mounted on a slide and observed under a fluorescence microscope (Olympus) equipped with fluorescence filter set for fluorescein isothiocyanate.The observed images were captured using a fluorescence filter and bright field (BF) with the CellSens Entry software (Olympus) and subsequently analyzed using image analysis software (Image-Pro Plus).The measured CP value was calculated as the ratio of the measured value (pixel) of the fluorescence image to the measured value (pixel) of the BF.The reduction rate of the measured CP value was calculated using the following formula:1.Measurement of CP = value measured using a fluorescent filter/ value measured using BF.

2 .
Reduction rate (%) of the measured CP value = ([CP measurement value before product application − CP measurement value after product application]/[CP measurement before product application value]) × 100.

F I G U R E 2
Figure 5.

F I G U R E 3
Effect of hyaluronic acid (HA) production by human dermal-derived fibroblasts (HDF) after treatment with three-dimensional adipocyte-derived mesenchymal stem cell-conditioned media (3D ADMSC-CM).F I G U R E 4Effects of antioxidation on three-dimensional adipocyte-derived mesenchymal stem cell-conditioned media (3D ADMSC-CM) cream.(A) Skin tone, (B) skin radiance.

3. 4 . 4 |
Evaluation of the moisturizing effect of 3D ADMSC-CM under extreme cold and dry weather conditionsWhen the moisture content of the skin decreases, phenomena that accelerate skin aging, such as itching and wrinkle formation, occur.