FormalPara Key Summary Points

Why carry out this study?

Stretch marks affect over half of pregnant women and can lead to a negative self-image, thus impacting their quality of life. Many risk factors that cause stretch marks are difficult to control during pregnancy; therefore, an effective and tolerable treatment modality is required.

This study aimed to evaluate the efficacy and safety of using a nanofractional radiofrequency machine, in combination with a topic formulation containing beta-glucan, in treating stretch marks.

What was learned from the study?

The current study shows that nanofractional radiofrequency machine usage, in combination with a topic formulation containing beta-glucan, may provide an effective, well-tolerated treatment option for stretch marks.

Introduction

Stretch marks, also termed striae distensae or striae gravidarum, are characterized by epidermal and dermal atrophy, manifesting as ordinary disfiguring scars [1]. Stretch marks initially appear as striae rubrae, which are erythematous and purplish, followed by the gradual appearance of striae albae, which lose their pigmentation and become pearlescent white [2]. Striae are prevalent skin alterations from prolonged exposure to steroids, endocrine skin conditions, and sudden weight gain [3]. During pregnancy, striae are the most prevalent connective tissue modifications commonly occurring after the 24th week [4]. Approximately 50–90% of pregnant women suffer from striae [5, 6]. Stretch marks can be disfiguring; moreover, patients may feel embarrassed or ashamed, which decreases their quality of life [6,7,8,9].

Histopathologically, early-stage stretch marks are characterized by the collagen bundles separation and disfigured collagen fibrils that fail to develop bundles [10]. Further, there is a marked disruption of the elastic fiber network, with the emergence of freshly synthesized tropoelastin-rich fibrils, possibly due to the uncoordinated synthesis of the elastic fiber components [11]. Stretch mark formation and atrophy are promoted by the continuous disruption of elastic fibers and collagenous extracellular matrix.

To reduce the risk of stretch mark formation, there have been several studies on the risk factors for the occurrence of stretch marks. Independent risk factors for stretch marks in primiparous women include positive family history, abdominal girth, uterine height, increased pre-pregnancy and pre-delivery weight, body mass index gain, young maternal age, and weight gain during pregnancy [12,13,14,15]. As many of these risk factors, including positive family history, are difficult to avoid during pregnancy, preventing stretch marks is challenging.

With improvements to their quality of life, an increasing number of women are concerned about stretch mark treatments. Several treatment strategies have been investigated, including the topical application of various creams or oils [16, 17], superficial dermabrasion [18], trichloroacetic acid peel [19], platelet-rich plasma [19], radiofrequency (RF) [20,21,22], and laser therapy [1, 4, 23]. The use of cosmetics only improves the appearance of skin wrinkles; it cannot eliminate or reduce their size [16]. Moreover, superficial dermabrasion is mainly aimed at the early pink or purple stretch marks, mainly inflammatory changes in stretch marks [18]. Additionally, strict control of the concentration and duration of action is required for trichloroacetic acid peeling as higher concentrations of tricarboxylic acid may “burn” the skin, making it more likely to produce hypopigmentation and potential scarring [24]. The use of platelet-rich plasma alone poses a risk of worsening stretch marks; generally, treatment is combined with microneedling and microdermabrasion, with bruising as a side effect [25]. Further, radiofrequency is effective for treating striae rubrae and striae albae [20, 22, 26]; the side effects are generally short-term erythema and edema [25], with no adverse events reported for patients with darker skin color (Fitzpatrick type IV and V) [27]. Fractional CO2 laser treatment is effective for both striae rubrae and striae albae, but its most prominent adverse reaction is postinflammatory hyperpigmentation [28]. In addition, pulsed dye laser is mainly used for new striae rubrae and may not be capable of eliminating scar-like texture and atrophy associated with striae albae. Moreover, patients with Fitzpatrick skin type IV-VI may have an increased risk of pigmentation [27]. Further, Nd:YAG laser is mainly used to treat striae rubrae; however, its effect on striae albae is not obvious [29].

Although some current treatment methods have achieved some positive results in improving stretch marks, the treatment of striae albae is still a huge challenge, and the side effects cannot be ignored [30]. To explore a better treatment for striae albae, and considering that Asian patients generally have Fitzpatrick skin types III–IV according to literature reports, RF can be applied to people with darker skin colors. Moreover, the study by Pongsrihadulchai et al. demonstrated that the treatment of striae albae using the equipment studied in this trial alone is effective and safe [21]. Since stretch mark occurrence is related to changes in the composition of the extracellular matrix, including fibrin, elastin, and collagen II, there may be minor wounds after instrument treatment. It has been reported that beta-glucans promote stimulation, the production of collagen and elastin, and wound healing [31, 32]. Therefore, we have designed a scheme to treat striae albae by Venus Viva and topical formulations containing beta-glucan. In this study, four groups were established to compare the effects of products used alone, instrument-combined topical formulations containing beta-glucan, and instrument-combined matrix formulations.

Venus Viva, a fractional RF machine equipped with two applicators (Venus Viva MD and DiamondPolar), was used as the therapeutic device in our study. This device uses proprietary SmartScan and advanced NanoFractional RF technologies to accurately control the pattern generation and heated-region density throughout the therapy; it is an alternative to microneedling and fractional laser treatments. Additionally, NanoFractional RF technology uses sharp pins like an electrode to deliver RF energy directly to the skin through a fractionation technique [21]. The energy is emitted through 160 pins/tip (62 mJ/pin), and the footprint caused by the microneedle is small (150 × 20 µm).

Therefore, this study aimed to investigate the efficacy of a new treatment for stretch marks made up of topical formulations containing beta-glucan combined with nanofractional radiofrequency.

Methods

Participants

We included 64 Chinese women aged 20–45 years at > 6 months after delivery with obvious white or silver abdominal stretch marks. Exclusion criteria included a history of allergies to the test cosmetics and their ingredients or daily chemical products, abdominal cosmetic procedures (e.g., laser surgery, platelet-rich plasma injection, or topical tretinoin) within the last 3 months, active abdominal skin diseases (e.g., infection, eczema, psoriasis, or skin cancer), and a follow-up period of < 12 weeks. This study was approved by the Biomedical Ethics Committee of West China Hospital, Sichuan University (trial registration number: ChiCTR2200056725). The study was conducted in accordance with the 1964 Declaration of Helsinki. All participants provided a signed informed consent form.

Study Design

This was a randomized, single-blind, controlled trial. Participants were randomly allocated to four groups and followed up for 3 months. Randomization was conducted using computer-based random allocation software. Group A was set as the control group and received no treatment. Group B was treated twice daily with topical formulations containing beta-glucan. Group C was treated twice daily with topical formulations containing beta-glucan combined with the Venus Viva MD applicator, which was applied at baseline (week 0), week 4, and week 8, and the DiamondPolar applicator, which was applied at weeks 2 and 6. Group D was treated twice daily with matrix formulations without beta-glucan combined with both applicators at the aforementioned time points. Participants in groups A and B were not blinded. All participants in groups C and D were blinded to whether they received product or matrix formulation. The therapist was not blinded, whereas the investigators and instrument operators were blinded to study-group assignments.

Objective Assessments

At baseline, the target stretch mark was selected on the abdomen of each participant and labeled for reference. The same stretch mark was evaluated during each follow-up evaluation. Examinations were performed at baseline and weeks 2, 4, 8, and 12. We measured the following parameters for stretch marks: width, measured using a vernier caliper (Mitutoyo Corporation, Kawasaki, Japan), with the measurement unit of width being centimeter (cm); elasticity, measured using a Cutometer MPA580 (Courage and Khazaka Electronic GmbH, Cologne, Germany), with the parameter Q1 being recorded for skin elasticity, which represents total recovery and is represented by the ratio of the elastic recovery area (QE) divided by the maximum recovery area (Q0) [33] and as such is not expressed in units, the closer the Q1 was to 1, the better the elasticity [34]; skin color was examined using the Chroma Meter CM2600d (Minolta Camera Co. Ltd., Osaka, Japan) and the associated values are expressed in CIE (Commission International d’Eclairage) L*, a*, b* units [35, 36], with the L* value representing skin brightness, with larger values indicating pronounced skin whiteness and the a* values representing the degree of redness and greenness, with larger values indicating more skin redness; and skin thickness and collagen density were evaluated using DermaLab Combo (Cortex Technology, Hadsund, Denmark), with larger test values indicating greater skin thickness in micrometers (µm) and collagen density. The intensity measured by this instrument represents collagen density, which is not expressed as units [37]. Test-area stretch marks were photographed before treatment and at each follow-up visit using a Canon EOS 450D camera (Canon Inc., Tokyo, Japan).

Subjective Assessments

Two trained assessors blinded to the treatment protocol independently rated the severity, color, outline, and relaxation of the striae using a 4-point clinical scale (0, no striae; 1, slight; 2, moderate; and 3, severe). The percentage of the abdominal surface area covered by striae was recorded on a 0–6-point scale (0, no striae; 1,  < 10%; 2, 10–29%; 3, 30–49%; 4, 50–69%; 5, 70–89%; and 6,  > 90%).

At each follow-up visit, the doctor evaluated and recorded whether the patient’s treatment area had symptoms such as erythema, edema, and pigmentation. Before treatment, patients were informed that short-term erythema, edema, or even crusting may occur after treatment. Generally, if the patient did not recover after 10 days, they were instructed to contact us. We stated that if blisters, infections, or pigmentation occurred, they should please contact us immediately.

Treatment

The Venus Viva (Venus Concept, Toronto, Canada) was applied in this study. Treatment was administered after objective and subjective assessments at weeks 0, 4, and 8. At 60 min before treatment, the abdomen was cleaned, and an anesthetic cream was applied. The abdomen was then sterilized using povidone-iodine. Abdominal stretch marks were treated using the Venus Viva MD applicator. Treatment parameters, 23–27 ms pulse width and 265–280 V, were customized according to the individual’s stretch mark status. After treatment, group C was treated with topical formulations containing beta-glucan, in which a film was applied for 20 min. Group D was treated with matrix formulations without beta-glucan, and the film was applied for 20 min.

The DiamondPolar applicator treatment, a multipolar RF magnetic pulse that heats the skin at a temperature of 41–43 °C, was performed after assessments at weeks 2 and 6 for approximately 25 min.

Statistical Analyses

All data are presented as mean ± standard deviation. Comparisons of measurements at various time points and baseline values were performed using a one-way analysis of variance. Inter-group comparisons of measurements at the same time point were performed using a two-sample t-test. Statistical analyses were performed using SPSS 23.0 (SPSS, Inc., Chicago, IL, USA). Statistical significance was set at a P-value of < 0.05.

Results

A total of 64 participants (16 participants per group) received the treatments. One participant had Fitzpatrick skin type II, 11 had type III, and 4 had skin type IV in group A. Two participants had Fitzpatrick skin type II, 13 had type III, and 1 had skin type IV in group B. One participant had Fitzpatrick skin type II, 13 had type III, and 2 had skin type IV in group C. One participant had Fitzpatrick skin type II, 14 had type III, and 1 had skin type IV in group D. None were excluded from the trial due to a lack of efficacy or adverse reactions.

Stretch Mark Width

Compared with the baseline measurements, group A showed no efficacy; in contrast, groups B and C showed significant efficacy from weeks 8 to 12, and group D showed significant efficacy at week 12 (Fig. 1i). Compared with group A, groups B and D showed a greater reduction in the stretch mark width from weeks 4 to 12, whereas group C showed a mild significant reduction from weeks 2 to 12. In addition, compared with group B, group C showed a significant reduction in the stretch mark width at weeks 2 and 12, whereas group D showed no significant difference. In addition, there was a significant difference in the stretch mark width between groups C and D from weeks 8 to 12 (Fig. 1ii).

Fig. 1
figure 1

Changes in stretch mark width. (i) Time point contrasts compared with the baseline values. (ii) Between-group comparisons, differences are adjusted by baseline values (*P < 0.05)

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Skin Elasticity

Compared with the baseline measurements, group A showed no efficacy, whereas groups B, C, and D showed significant efficacy from weeks 2 to 12, 4 to 12, and 8 to 12 (Fig. 2i), respectively. Further, compared with group A and on the basis of the Q1 parameter, group B showed significant efficacy from weeks 2 to 12, whereas groups C and D showed significant efficacy from weeks 4 to 12. Compared with group B, groups C and D showed a significant increase in Q1 at week 12. Additionally, compared with group D, group C showed a significant decrease in Q1 (Fig. 2ii).

Fig. 2
figure 2

Changes in skin elasticity. (i) Time point contrasts compared with the baseline values. (ii) Between-group comparison, differences are adjusted by baseline values (*P < 0.05)

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Skin Thickness and Collagen Density

Compared with the baseline values, groups A and B showed no efficacy from weeks 2 to 12 regarding skin thickness and collagen density, whereas group C showed significant efficacy from weeks 4 and 12 regarding collagen thickness. As for the collagen density, group C showed significant efficacy at weeks 4, 8, and 12. Group D showed a gradual increase in skin thickness and collagen density, with significant efficacy achieved at week 12 (Fig. 3i–ii).

Fig. 3
figure 3

Changes in skin thickness and collagen density value. (i) Skin thickness for time point contrasts compared with the baseline values. (ii) Collagen density for time point contrasts compared with the baseline values. (iii) Between-group comparison in skin thickness, differences adjusted by baseline values. (iv) Between-group comparison in collagen density, differences adjusted by baseline values (*P < 0.05)

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Compared with group A, group B showed a significantly higher increase in the collagen density from weeks 2 to 12; however, there was no intergroup difference in skin thickness. Compared with group A, group C showed a significant increase in skin thickness at weeks 4 and 12, and a significant increase in collagen density at weeks 4, 8, and 12. Similarly, compared with group A, group D showed a significant increase in collagen density at week 12; however, there was no change in skin thickness.

Compared with group B, group C showed a significant increase in skin thickness at weeks 4 and 12, and in collagen density at week 12. Compared with group D, group C showed a significant decrease in the skin thickness at week 12, and in collagen density at weeks 4, 8, and 12 (Fig. 3iii–iv).

Skin Color

No significant differences were observed between groups A and B in the L* and a * values at weeks 2, 4, 8, and 12. Compared with the baseline values, group C showed significantly lower L* values at weeks 8 and 12. In addition, compared with the baseline values, group C showed significantly increased a* values at weeks 2, 4, 8, and 12. Similarly, compared with the baseline values, no significant difference was observed in L* values in group D at weeks 2, 4, 8, and 12; however, there was an increase in a* values, which reached significance at weeks 2 and 4 (Fig. 4i–ii).

Fig. 4
figure 4

Changes in L* and a* value. (i) L* value for time point contrasts compared with the baseline values. (ii) a* value for time point contrasts compared with the baseline values. (iii) Between-group comparison in the L* value, differences were adjusted by baseline values. (iv) Between-group comparison in the a* value, differences adjusted by baseline values. (*P < 0.05)

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There were no significant differences in L* values between groups A and B. Compared with Group A, Group C showed a significant decrease in the L* value at weeks 2, 4, and 12, and a significant increase in a* values at weeks 2 and 4. In addition, compared with group A, group D showed a significant decrease in L* values at week 2, and a significant decrease in a* values at weeks 2 and 4.

Furthermore, compared with group B, group C showed a more significant decrease in L* values at weeks 2, 8, and 12, and a more significant increase in a* values at weeks 2, 4, 8, and 12. Compared with group B, group D showed a more significant decrease in the L* value at weeks 2 and 8, and a more significant increase in a* values.

Compared with group D, group C showed a more significant increase in a* values at weeks 2 and 12; however, there were no significant intergroup differences in L* values (Fig. 4iii–iv).

Stretch Marks Photograph

Typical stretch mark photo of one participant in each of the four groups before and after treatment.

Safety

Participants experienced erythema and, in some cases, slight bleeding after treatment. After 24 h, the skin developed several pointy scabs the approximate size of pinheads. Generally, 7–10 days later, the scabbed skin fell off by itself. All side effects were self-limited and resolved without treatment. In addition, postinflammatory pigmentation was not reported in any patients, and no participant withdrew because of adverse effects.

Discussion

Although stretch marks do not affect health, they cause a psychological burden to many pregnant women. There has been extensive research on stretch mark treatment and prevention; however, the efficacy of available treatment strategies remains unsatisfactory [12, 13, 38]. This study showed an excellent effect after using beta-glucan twice daily combined with microneedling, which was applied at weeks 0, 4, and 8, and RF, applied at weeks 2 and 6. Our treatment repaired stretch marks, increased elasticity, and improved the color.

We assessed treatment outcomes using noninvasive evaluation techniques. Specifically, we evaluated the stretch mark width, skin elasticity, skin thickness, collagen density, and skin color. Skin elasticity was evaluated using the Cutometer MPA580, which assesses the viscoelastic properties of human skin through the suction approach [39]. Skin thickness and collagen density were measured using the DermLab Combo [40]. Skin color was evaluated using the CM2600d with L*a*b* measurements [41].

Compared with the other groups, group C significantly improved the stretch mark width, skin elasticity, skin thickness, collagen density, and skin color. Beta-glucan is a high-purity polysaccharide obtained from chlorella grown from rotten marine wood after biological fermentation and purification. It has multiple properties, including tumor suppression, immunity activation, anti-aging effects, anti-allergy effects, and intestinal flora stabilization [31, 42]. However, the use of beta-glucan for stretch mark treatment remains unclear.

After being recognized and captured by Langerhans cells, beta-glucan promotes collagen synthesis as well as the division and proliferation of skin cells through a series of biological transductions [32, 43]. Langerhans cells initiate a series of reactions in the skin with the stimulation and differentiation of macrophage colony-stimulating factors to cause fibroblast activation [43]. This produces cytokines, such as interleukin-1, interleukin-6, interleukin-15, granulocyte-macrophage colony-stimulating factor, epidermal cell growth factor, and vascular growth factor, which promote wound healing and collagen production, reaggregate collagen and elastic fibers, and improve the skin condition internally [43, 44].

Beta-glucans stimulate macrophages, fibroblasts, keratinocytes, lymphocytes, and other important cells to activate, proliferate, migrate, and release various cytokines, thus enhancing cell function [43]. Additionally, beta-glucans have antiinflammatory and bacteriostasis effects and facilitate collagen synthesis, granulation tissue growth, wound reepithelialization, and reconstruction after wound healing, which promotes wound healing [31, 32]. In group B, which only received beta-glucans, a significant improvement was observed in the stretch mark width and skin elasticity compared with group A and baseline values, indicating the wound healing and collagen synthesis abilities of beta-glucans.

Several studies have investigated stretch mark treatment using RF [20,21,22] and microneedling [19, 23, 45, 46]. However, no studies have investigated stretch mark treatment using RF combined with microneedling. The Venus Viva system is a tool used for several esthetic manifestations, including improving traumatic and acne scars [47, 48]. This device uses proprietary SmartScan and advanced NanoFractional RF technologies to facilitate accurate control over the unique pattern generation and heated region density throughout the therapy, allowing reproducible clinical outcomes and homogeneous treatments. The energy transported to each micropin maximizes patient comfort and ensures uniform tissue treatment, producing consistent, homogeneous, and reproducible clinical results.

Compared with group A and baseline values, group D showed a greater decline in the stretch mark width and improvements in skin elasticity and collagen density. Although group D had a lower effect than group C, it showed efficacy in treating stretch marks (Fig. 5).

Fig. 5
figure 5

Photo of typical stretch marks for one participant in each of the four groups before and after treatment

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Stretch marks represent a disfiguring condition with only esthetic effects; however, histological examination in patients is difficult. Noninvasive evaluation techniques are convenient and can effectively evaluate the therapeutic effects of stretch marks. Our findings showed that treatment using beta-glucans combined with RF and microneedling showed treatment efficacy.

This study had some limitations. First, the number of patients in each group was small. Due to the limited sample size, we intend to expand the number of participants in future studies. Second, the treatment course only lasted 3 months, and a longer treatment period may have been more effective.

In conclusion, according to the experimental results, group C, which was treated with topical formulations containing beta-glucan twice daily combined with the Venus Viva MD applicator three times in total and the DiamondPolar applicator two times in total, had the greatest effect. This method significantly reduces the stretch mark width and increases the elasticity, skin thickness, and collagen density of stretch marks.

Further studies should evaluate the frequency of the device use and set parameters to maximize the therapeutic effect of stretch marks and minimize the risk.

Conclusion

Our results indicate that treatment using topical formulations containing beta-glucan, combined with nanofractional radiofrequency plus magnetic nanofractional radiofrequency, is effective and tolerable for women with stretch marks.