CO2 Fractional Laser Combined with 5-Fluorouracil Ethosomal Gel Treatment of Hypertrophic Scar Macro-, Microscopic, and Molecular Mechanism of Action in a Rabbit Animal Model.

The treatment of hypertrophic scar (HS) has thus far been a clinical challenge. We evaluated the therapeutic effect of CO₂ fractional laser combined with 5-fluorouracil ethosomal gel (5-FU EG) in rabbit HS model. HS model was established as standardized scars on the ventral surface of rabbit ears, divided into four groups: control (no intervention), EG treatment, laser treatment, and combined treatment group (laser plus 5-FU EG). Clinical macroscopic and H&E-stained microscopic observations were conducted to assess HS improvement. The mRNA levels of types I and III collagen, transforming growth factor-β1 (TGF-β1), and interleukin-6 (IL-6) were detected by real-time PCR. After 14 days, H&E staining shows that the thickness of HS in treatment groups was significantly lower compared with the control group, and the thickness in laser treatment group and combined treatment group was significantly lower compared with the EG treatment group. The mRNA levels of types I and III collagen, TGF-β1 were significantly low in all treatment groups, whereas IL-6 was highest in the laser treatment group at day 14. The macro- and microscopic effects of the combined and CO₂ fractional laser treatment were better compared with 5-FU EG only. Inhibition of types I and III collagen, TGF-β1 are the possible underlying mechanism of action, whereas the function of IL-6 remains to be further studied. Our study suggests that the effect of combined 5-FU EG and laser, as well as laser-only treatment are superior to 5-FU EG monotreatment. The mechanism of HS improvement is related to reduction of collagen I/III and the inhibition of TGF-β1 expression.