Efficacy and safety of recombinant human epidermal growth factor combined with fractional carbon dioxide laser for facial atrophic acne scars: a systematic review and meta-analysis of randomized trials

The combination of recombinant human epidermal growth factor (rhEGF) and fractional carbon dioxide (CO2) laser therapy is increasingly used in the treatment of facial atrophic acne scars. This study aimed to systematically assess the efficacy and safety of rhEGF combined with fractional CO2 laser therapy for managing facial atrophic acne scars. PubMed, Embase, the Cochrane Library, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang, SinoMed, and VIP were searched from inception to July 29, 2025. Parallel-group or split-face randomized controlled trials (RCTs) comparing fractional CO2 laser therapy + rhEGF with fractional CO2 laser therapy for treating atrophic acne scars were considered for inclusion. Risk of bias was assessed using the Cochrane Collaboration’s risk-of-bias tool. The meta-analysis based on fixed or random effects models was carried out for Echelle d’Evaluation Clinique des Cicatrices d’acne (ECCA) scores, Vancouver Scar Scale (VSS) scores, transepidermal water loss (TEWL), etc. It was registered on PROSPERO (ID: CRD42024599311). Twelve RCTs involving 1,044 patients were included, and all trials were conducted in China. Follow-up durations across studies ranged from 1 week to 12 months. Compared with fractional CO₂ laser therapy alone, the combination therapy significantly reduced ECCA scores by a mean of 11.14 points (95% CI: -16.82 to -5.45, P = 0.0001) and VSS scores by a mean of 1.54 points (95% CI: -2.55 to -0.54, P = 0.003). The combination therapy demonstrated advantages in improving the durations of crust formation. The incidence of adverse events, particularly hyperpigmentation (RR = 0.41, 95% CI: 0.20 to 0.86; P = 0.02), was significantly lower in the combination therapy group. According to the GRADE assessment, the certainty of evidence ranged from very low to moderate for most outcomes. This study suggests that rhEGF combined with fractional CO₂ laser therapy may be beneficial for treating atrophic acne scars. However, because of the low to moderate certainty of evidence according to GRADE assessment, more robust, large-scale RCTs are needed to confirm these findings and define optimal treatment parameters.