Abstract
To evaluate the impact of CO2 fractional laser combined with recombinant human epidermal growth factor (rhEGF) gel on skin barrier in acne scar patients. In a retrospective analysis, we examined 105 acne scar patients admitted between July 2018 and August 2021. Of these, 51 received only CO2 fractional laser (control group), while 54 underwent a combination of CO2 fractional laser and rhEGF gel (observation group). We assessed treatment efficacy, symptom relief, skin barrier parameters, pre- and posttreatment inflammatory factors, adverse reactions, posttreatment quality of life, and patient satisfaction. The observation group exhibited a higher overall response rate, significantly shorter wound healing, scab formation, and scab detachment times. Additionally, this group showed increased stratum corneum water content, decreased pH, and transdermal water loss (TEWL), and reduced hypersensitive C-reactive protein and interleukin-6 expression posttreatment. Quality of life scores were higher, with fewer adverse reactions and greater treatment satisfaction. Combining CO2 fractional laser with rhEGF gel markedly improves acne scar treatment efficacy, enhances skin barrier function, reduces inflammation, and elevates quality of life. Its safety profile supports its broader clinical adoption.
Keywords: acne scars, CO2 fractional laser, recombinant human epidermal growth factor gel, skin barrier
1. Introduction
Acne, a condition primarily affecting adolescents, is characterized by a multifaceted pathogenesis driven by factors such as increased sebaceous gland activity, elevated androgen levels, and infection by Propionibacterium acnes.[1,2] These factors constitute crucial etiological components contributing to the disease’s onset. Acne scars, on the other hand, represent the lingering aftermath of severe acne inflammation or inadequately managed acne lesions, significantly impacting patients’ social interactions, psychological well-being, physical appearance, and even their prospects in marriage and employment.[3,4] As living standards continue to rise, the pursuit of beauty has become an essential aspiration for individuals once their material needs are met. Effectively addressing acne scars presents a contemporary challenge in the realm of skin rejuvenation, demanding immediate clinical attention.[5]
Currently, numerous clinical approaches are available for treating patients with acne scars, with fractional laser therapy being widely employed as the preferred option for addressing acne pitting scars due to its favorable outcomes and high safety profile.[6] Nonetheless, the utilization of CO2 fractional laser surgery has been associated with several reported complications, including postinflammatory pigmentation, prolonged erythema, and scarring.[7] Furthermore, the treatment of acne pitting scars often necessitates multiple sessions, imposing a substantial psychological and economic burden on patients.[8] Consequently, the focus of clinical research has shifted toward strategies aimed at reducing adverse reactions associated with CO2 fractional laser surgery while simultaneously enhancing its therapeutic efficacy. Recombinant human epidermal growth factor (rhEGF), a highly purified multifunctional growth factor produced through gene recombination technology, exhibits properties such as the activation of intracellular DNA topoisomerase, promotion of gene expression related to cell proliferation, and regulation of protein synthesis. These attributes enable rhEGF to initiate and expedite the repair of skin tissue with minimal toxic side effects.[9] Despite this, there remains a paucity of studies investigating the combined effects of CO2 fractional laser therapy and rhEGF on acne scar patients, particularly concerning their impact on inflammatory factors.
The aim of this study was to observe the effect of CO2 fractional laser combined with rhEGF on the skin barrier and serum hypersensitive C-reactive protein (hs-CRP) in patients with facial acne scars, in order to provide more ideas for the selection of treatment options for patients with acne scars.
2. Materials and methods
2.1. Clinical data
We collected clinical data from 201 patients who underwent acne scar treatment in our hospital from July 2018 to August 2021. According to the established inclusion criteria: Patients aged 18 to 32 years; patients with complete clinical data. Exclusion criteria: Patients with skin tumors; patients with liver, kidney, and other important organ dysfunction; patients with severe infectious diseases and immune dysfunction; pregnant women and lactating patients. In the end, 105 cases were successfully enrolled. Fifty-one patients received CO2 fractional laser treatment (control group), and another 54 patients received CO2 fractional laser combined with rhEGF gel treatment (observation group). This study had been approved by the hospital ethics committee and conformed to the Declaration of Helsinki.
2.2. Treatment method
All patients underwent CO2 fractional laser therapy using the Wuhan Qizhi Laser Technology Co., Ltd., Model 2030CI, applied to their facial region. The laser settings were configured with a wavelength of 10.6 μm, fractional coverage rate ranging from 1.86% to 2.18%, pulse width not exceeding 400 μs, and a light wave diameter measuring between 0.1 and 0.4 mm. Prior to treatment, the afflicted area was meticulously cleansed, followed by the application of a compound lidocaine cream (Tongfang Pharmaceutical Group Co., Ltd., GYZZ H20063466). One hour later, the anesthetic agents were removed, and a skin spot test was conducted. Laser irradiation parameters were suitably adjusted based on the extent of skin damage, with the optimal settings achieved when uniform erythema appeared on the face. During the laser treatment, the repetition of irradiation in the same area was avoided, and a total of 3 treatment sessions were performed, each separated by a 6 to 8-week interval.
On this basis, patients in the observation group were treated with rhEGF applied to the affected area 3 times a day for 2 weeks, the patients in the control group applied gel of equivalent texture or placebo to the affected area. Strict sun protection and scientific skin care should be conducted after surgery. After each treatment, the treatment parameters were recorded in detail. Immediately after the end of treatment and within 7 days after treatment, the patients were asked to update with photos taken in affected area daily and to describe the corresponding symptoms, and were informed of the time of desquamation and the time of erythema subsidence after desquamation. The treatment was performed every 3 months. At the end of the third treatment, the patients were followed up after 3 months of recovery.
2.3. Outcome measures
Therapeutic effect was evaluated and compared among patients treated for 2 weeks, and was categorized as follow – Cure: scar repair ≥ 80%, flat new skin, and normal skin color; Markedly effective: 60% ≤ scar repair < 80%, flat new skin, but with slight dark subsidence on the skin; Effective: 40% ≤ scar repair < 60%, with obvious dark subsidence on the skin; Ineffective: scar repair < 40% or not significant, and with no signs of pigmentation dissipating. Treatment response rate = (recovered + significantly effective + effective)/total number of cases × 100%.
The symptom relief time (including wound healing time, scab formation time, and scab detachment time) was recorded and compared between the 2 groups.
Skin barrier-related parameters were measured and compared between the 2 groups, and transdermal water loss (TEWL), pH, and stratum corneum water content were measured using TM 300, pH 900, and CM 825, respectively, after 30 minutes in a constant humidity and constant temperature environment.
Acne scar comprehensive scores (ECCA) were compared before and after treatment, assessing scar shape and density. The scoring included the following criteria: V-type, diameter >2 mm, punctate distribution, scored as 15 points; U-type, diameter 2 to 4 mm, steep edges, scored as 20 points; M-type, diameter above 4 mm, irregular distribution, scored as 25 points; the number of scars, with fewer than 5 counted as 1 point, 5 to 20 as 2 points, and above 20 as 3 points, with the final score calculated as the product of the 2.
Inflammatory factor levels were compared between the 2 groups before and after treatment. Five milliliters of fasting venous blood was drawn from the 2 groups before and after treatment, and the supernatant was rapidly separated by centrifugation at 3500 r/minutes for 10 minutes. Serum hs-CRP and interleukin-6 (IL-6) levels were measured by ELISA.
The incidence of adverse reactions during treatment were recorded and compared between the 2 groups, including dry skin, muscle pain, dry lips, and facial desquamation.
Life quality of patients in the 2 groups were assessed 2 months after treatment using SF-36[10] scale, and the higher the scores of each assessment, the better the quality of life.
Treatment satisfaction of the 2 groups of patients were assessed and compared, which was divided into very satisfied, satisfied, and dissatisfied. Satisfaction rate = (very satisfied cases + satisfied cases)/total cases × 100%.
3. Statistical methods
The study used SPSS20.0 software to analyze the collected data, and used GraphPad Prism 8 software to visualize the collected data. Among them, Student t test and Paired t test was used for intergroup comparison and intragroup comparison, respectively, expressed as t. Chi-square test was used for enumeration data. Statistical differences were indicated when P < .05.
4. Results
4.1. General data comparison
Subjects were comparable because there were no evident differences identified in gender, age, and BMI between the 2 groups (P > .05, Table 1).
Table 1.
Comparison of general data.
| Variable | Observation group (n = 54) | Control group (n = 51) | t/χ2 | P |
|---|---|---|---|---|
| Gender | 0.025 | .873 | ||
| Male | 32 (59.26) | 31 (60.78) | ||
| Female | 22 (40.74) | 20 (39.22) | ||
| Age (yr) | 26.23 ± 1.24 | 25.94 ± 1.26 | 1.188 | .237 |
| BMI (kg/m2) | 22.17 ± 1.51 | 22.49 ± 1.39 | 1.128 | .262 |
| Smoking history | 0.078 | .780 | ||
| Yes | 29 (53.70) | 26 (50.98) | ||
| No | 25 (46.30) | 25 (49.02) | ||
| Alcohol history | 0.002 | .964 | ||
| Yes | 32 (56.26) | 30 (58.82) | ||
| No | 22 (40.74) | 21 (41.18) | ||
| Disease duration (yr) | 0.003 | .955 | ||
| ≥1 | 31 (57.41) | 29 (56.86) | ||
| <1 | 23 (42.59) | 22 (43.14) | ||
| Skin type | 0.008 | .929 | ||
| Fitzpatrick III | 26 (48.15) | 25 (49.02) | ||
| Fitzpatrick IV | 28 (51.85) | 26 (50.98) |
BMI = body mass index.
4.2. Comparison of treatment efficacy between the 2 groups
The ORR of the observation group was evidently higher than that of the control group (96.30% vs 76.47%, Table 2).
Table 2.
Comparison of efficacy between the 2 groups [n (%)].
| Efficacy | Observation group (n = 54) | Control group (n = 51) | χ2 | P |
|---|---|---|---|---|
| Cured | 25 (46.30) | 10 (19.61) | – | – |
| Markedly effective | 17 (31.48) | 16 (31.37) | – | – |
| Effective | 10 (18.52) | 13 (25.49) | – | – |
| Ineffective | 2 (3.70) | 12 (23.53) | – | – |
| Overall response rate | 52 (96.30) | 39 (76.47) | 8.922 | .003 |
4.3. Comparison of time to symptom relief between the 2 groups
The wound healing time, scab formation time, and scab detachment time in observation group were markedly lower than those in control group (P < .05), indicating that the patients in observation group recovered faster (Table 3).
Table 3.
Comparison of symptom relief time between the 2 groups.
| Item | Observation group (n = 54) | Control group (n = 51) | t | P |
|---|---|---|---|---|
| Wound healing time | 8.76 ± 0.43 | 12.88 ± 1.12 | 25.15 | <.001 |
| Scab formation time | 2.55 ± 0.26 | 4.77 ± 0.44 | 31.68 | <.001 |
| Scab detachment time | 6.62 ± 0.39 | 9.59 ± 0.91 | 21.95 | <.001 |
4.4. Comparison of ECCA scores between the 2 patients before and after treatment
Before treatment, there was no significant difference in ECCA scores between the 2 groups (P > .05). After treatment, the ECCA scores significantly decreased in both groups, but the improvement was more pronounced in the observation group compared to the control group (P < .05, Table 4).
Table 4.
Comparison of ECCA scores between the 2 patients before and after treatment.
| Item | Observation group (n = 54) | Control group (n = 51) | t | P |
|---|---|---|---|---|
| Before treatment | 67.43 ± 4.22 | 67.55 ± 4.21 | 0.146 | .884 |
| After treatment | 29.85 ± 2.13 | 36.74 ± 2.55 | 15.06 | <.001 |
4.5. Comparison of skin barrier-related indicators between the 2 groups
After treatment, TEWL and pH values in the 2 groups were both lower than those before treatment, and those in the observation group was lower than the control group; while stratum corneum water content was increased, and it was comparatively higher in observation group than in control group (P < .05, Fig. 1).
Figure 1.
Comparison of skin barrier-related indicators between the 2 groups. (A) Comparison of TEWL between the 2 groups. (B) Comparison of pH values between the 2 groups. (C) Comparison of stratum corneum water content between the 2 groups. *P < .05. TEWL = transdermal water loss.
4.6. Comparison of serum inflammatory factors before and after treatment between the 2 groups
Serum hs-CRP and IL-6 levels in the 2 groups both decreased after treatment, and those in observation group was lower than those in control group (all P < .05, Fig. 2).
Figure 2.
Comparison of serum inflammatory factors before and after treatment between the 2 groups. (A) Comparison of serum hs-CRP between the 2 groups. (B) Comparison of serum IL-6 between the 2 groups. *P < .05. hs-CRP = hypersensitive C-reactive protein.
4.7. Comparison of incidence of adverse reactions during treatment
The incidence rate of adverse reactions in observation group was 5.56%, which was markedly lower than that in control group (29.41%, P < .05, Table 5).
Table 5.
Adverse reactions comparison.
| Efficacy | Observation group (n = 54) | Control group (n = 51) | χ2 | P |
|---|---|---|---|---|
| Dry skin | 1 (1.85) | 3 (5.88) | – | – |
| Muscular pain | 1 (1.85) | 3 (5.88) | – | – |
| Dry lips | 0 | 4 (7.84) | – | – |
| Facial desquamation | 1 (1.85) | 5 (9.80) | – | – |
| Overall incidence comparison | 3 (5.56) | 15 (29.41) | 10.51 | .001 |
4.8. Comparison of quality of life after treatment between the 2 groups
After treatment, all quality of life scores in control group were evidently lower than those in observation group, indicating patients in observation group were assessed with better quality of life (P < .05, Table 6).
Table 6.
Comparison of incidence rate of SF-36 score after treatment between the 2 groups.
| Item | Observation group (n = 54) | Control group (n = 51) | t | P |
|---|---|---|---|---|
| Social functioning | 76.62 ± 2.17 | 62.39 ± 2.75 | 21.22 | <.001 |
| Mental status | 73.02 ± 2.37 | 67.22 ± 2.06 | 13.35 | <.001 |
| Health status | 91.86 ± 2.21 | 80.79 ± 1.92 | 27.33 | <.001 |
| Emotional function | 85.69 ± 2.09 | 72.96 ± 2.12 | 30.98 | <.001 |
4.9. Comparison of treatment satisfaction between the 2 groups
After treatment, the treatment satisfaction rate of the observation group was markedly higher than that of the control group (P < .05, Table 7).
Table 7.
Comparison of treatment satisfaction between the 2 groups.
| Satisfaction | Observation group (n = 54) | Control group (n = 51) | χ2 | P |
|---|---|---|---|---|
| Very satisfied | 30 (55.55) | 14 (27.45) | – | – |
| Satisfied | 22 (40.74) | 23 (45.10) | – | – |
| Not satisfied | 2 (3.70) | 14 (27.35) | – | – |
| Treatment satisfaction | 52 (96.30) | 37 (72.55) | 11.45 | <.001 |
5. Discussion
Acne, a prevalent chronic skin ailment among adolescents, often results from an aberrant surge in androgen secretion, triggering the overproliferation of P. acnes and hyperkeratosis of pilosebaceous ducts. This cascade of events culminates in the obstruction of hair follicles and an ensuing inflammatory response.[11] Additionally, genetic, immune, dietary factors, and lifestyle choices may also contribute to its pathogenesis.[12] Acne scarring, a common cosmetic concern stemming from acne, while generally not compromising skin function, profoundly impacts patients’ quality of life and psychological well-being. Thus, it is imperative to investigate rational and efficacious therapeutic strategies for managing acne scars, given their significant clinical relevance.
In this study, we evaluated the effectiveness of combining CO2 fractional laser with rhEGF for treating facial acne scars. Firstly, regarding treatment effectiveness, patients who underwent the combined therapy exhibited a significantly higher overall response rate compared to those treated solely with CO2 fractional laser. Moreover, the healing time for wounds in the combined therapy group was notably shorter. To provide context, the CO2 fractional laser utilized in this study is a type of fractional photothermal laser. It delivers a minuscule laser beam to the skin, organized in a fractional pattern. Its primary interaction occurs with water in the skin tissue, generating numerous tiny thermal damage zones known as microthermal damage zones. These microthermal damage zones stimulate the repair and healing process of scars, promoting the proliferation, and rearrangement of dermal collagen and elastic fibers, thereby achieving therapeutic goals.[13,14] It is worth noting that the scar healing process may extend up to 3 to 6 months following laser treatment.[15] This minimally invasive technique boasts significant advantages, including substantial treatment depth, high energy output, evident efficacy, rapid scab recovery, and a low incidence of adverse reactions. However, evidence suggests a high recurrence rate and persistence of symptoms in the treated area following fractional CO2 laser therapy.[16] rhEGF, a single-chain polypeptide, possesses potent mitogenic and growth-promoting properties, influencing various tissue cells such as vascular endothelial and epidermal cells. It fosters epithelial cell proliferation, granulation tissue formation, and expedites wound healing. Additionally, rhEGF stimulates the synthesis and secretion of macromolecules like extracellular hyaluronic acid and collagen. This enhances skin hydrophilicity and facilitates moisture retention. Moreover, rhEGF forms a protective barrier on the wound surface, preventing bacterial infections.[17,18] Therefore, its application in conjunction with CO2 fractional laser treatment further augments therapeutic efficacy.
Patients with acne often exhibit increased sebum production in affected areas, disruption of the lipid layer between keratinocytes and the skin barrier, and heightened susceptibility to inflammatory reactions, exacerbating their condition.[19] Acne itself represents an inflammatory response. hs-CRP, a notably reactive protein in infections, directly mirrors bacterial and viral infection levels, while IL-6 serves as a cytokine that activates and regulates immune cells, conveying the patient’s inflammatory status.[20] In this study, we also compared skin barrier-related parameters and the expression of serum hs-CRP and IL-6 between the 2 groups. The results revealed that posttreatment, both groups exhibited decreased TEWL, lower pH values, reduced serum hs-CRP, and IL-6 levels, with the observation group exhibiting more significant reductions than the control group. Concurrently, stratum corneum water content increased, with the observation group displaying higher levels than the control group. This indicates that CO2 fractional laser combined with rhEGF treatment effectively enhances the skin barrier and mitigates the inflammatory response within the body. This is primarily attributed to rhEGF treatment postfractional CO2 laser therapy, which elevates skin keratin water content, fortifies resistance against microorganisms, and diminishes skin sensitivity, ultimately improving the skin barrier and ameliorating the inflammatory response within the body.[21,22] Posttreatment, the observation group exhibited a lower incidence of adverse reactions compared to the control group. This outcome is attributable not only to the implementation of scientifically grounded skincare practices, stringent sun protection, maintenance of wound cleanliness, and infection prevention measures but also underscores the advantages of rhEGF treatment. Finally, we assessed the quality of life and treatment satisfaction of both groups posttreatment. Patients in the observation group reported notably higher satisfaction levels than those in the control group. This discrepancy is closely linked to the superior efficacy and safety profile of CO2 fractional laser combined with rhEGF. It further underscores the clinical viability and rationale of this treatment approach.
In summary, fractional superpulse CO2 laser combined with rhEGF gel is effective in the treatment of acne scars and can effectively improve the skin physiological barrier function and inflammatory response in patients with high safety. It is worthy of being widely popularized in the clinical application. However, this study also has some limitations. First, due to the small sample size, the conclusions of this study remain to be further analyzed, and we will carry out multicenter large-sample studies to demonstrate our results; second, we did not follow-up and analyze the long-term prognosis of patients, so that their recurrence rate remains unknown. We will subsequently strengthen the follow-up of patients and further improve the data.
Author contributions
Conceptualization: Hua Wang.
Data curation: Hua Wang.
Funding acquisition: Fan Yang.
Investigation: Fan Yang, Jia He.
Methodology: Fan Yang, Jia He.
Project administration: Hui Wang.
Resources: Hui Wang, Tao Qin, Chan Zhao.
Software: Tao Qin.
Supervision: Chan Zhao.
Validation: Hua Wang, Chan Zhao.
Visualization: Hua Wang, Chan Zhao.
Writing – original draft: Hua Wang.
Writing – review & editing: Chan Zhao.
Abbreviations:
- hs-CRP
- hypersensitive C-reactive protein
- IL-6
- interleukin-6
- rhEGF
- recombinant human epidermal growth factor
- TEWL
- transdermal water loss
This study received funding from Shaanxi Health Research Project (No. 2022D015).
This study was reviewed and approved by the Baoji Hospital of Traditional Chinese Medicine Ethics Committee (BJSZYYY-LWTG-20230131).
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are publicly available.
How to cite this article: Wang H, Yang F, Wang H, Qin T, He J, Zhao C. Effect of CO2 fractional laser combined with recombinant human epidermal growth factor gel on skin barrier. Medicine 2024;103:11(e37329).
Contributor Information
Hua Wang, Email: Wh18015759254@163.com.
Fan Yang, Email: zwyyfww@163.com.
Hui Wang, Email: Wh18015759254@163.com.
Tao Qin, Email: 18609270039@163.com.
Jia He, Email: hj1125642579@163.com.
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