Synergistic Effects of Fractional CO 2 Laser and Recombinant Humanized Type III Collagen (rhCol III) in Atrophic Acne Scar Treatment: Activation of MAPK Pathway and Enhanced Collagen Remodeling

Background Fractional CO 2 laser (FCL) is widely used for resurfacing the skin with atrophic acne scars. This study aims to explore the synergistic efficacy of recombinant humanized type III collagen (rhCol III) on FCL in treating atrophic acne scars. Methods A total of 20 patients with facial atrophic acne scars from two medical institutions were treated with a single session of full‐face FCL. One month post‐FCL, they were randomly assigned to the FCL + rhCol III group and FCL + NC group, with 10 cases per group. Patients in the FCL + rhCol III group received dermal injections with 4 mg of rhCol III dissolved in 1.2 mL of saline on one side of the face, and those in the FCL + NC group were similarly injected with the same amount of saline. Dermal injections were performed three times, with an interval of 4 weeks. Therapeutic efficacy was assessed using the Echelle d’évaluation clinique des cicatrices d’acné (ECCA) grading scale and the Global Scarring Grading System (GSS). Human dermal fibroblasts (HDFs) were cultured in vitro, and induced with FCL and rhCol III. Immunofluorescence was utilized to detect the expression of type I and III collagens. RNA‐sequencing (RNA‐seq) identified differentially expressed genes (DEGs) in HDFs induced with FCL combined with rhCol III. Results A total of 18 eligible patients were enrolled and followed up. Post‐treatment, patients in the FCL + rhCol III group were graded with a significantly lower ECCA score (77.50 ± 15.07 vs. 106.1 ± 21.25, p < 0.05), but a higher scar improvement rate (40.23% ± 13.23% vs. 23.26% ± 19.69%, p < 0.05) than those in the FCL + NC group. Classified by the type of acne scars, patients with boxcar and icepick acne scars significantly benefited more from FCL combined with rhCol III than those in the FCL + NC group and showed a significantly reduced ECCA score and an increased scar improvement rate ( p < 0.05). Similarly, patients in the FCL + rhCol III group also exhibited significantly a lower GSS score (7.75 ± 1.75 vs. 10.00 ± 2.33, p < 0.05) and a higher scar improvement rate (43.30% ± 10.49% vs. 25.59% ± 18.34%, p < 0.05). In vitro experiments showed that the induction of FCL combined with rhCol III significantly upregulated type I and III collagens in HDFs. RNA‐seq unmasked that MAPK signaling pathway was activated in HDFs induced with FCL combined with rhCol III. Conclusion FCL combined with rhCol III effectively reduces facial atrophic acne scars through the activation of the MAPK pathway.