Comparison of combination therapy (steroid, calcium channel blocker, and interferon) with steroid monotherapy for treating human hypertrophic scars in an animal model.

Abstract

Hypertrophic scar (HSc) treatment continues to be a clinical challenge. To evaluate the efficacy of a combined regimen of calcium channel blocker (verapamil), steroid, and interferon in treating HSc. Ten excised human HSc fragments obtained from surgically treated burn patients were divided into 3 groups: A (no drug), B (steroid, 0.05 mL), and C (verapamil, steroid, and interferon, 0.016 mL each). These specimens were implanted on the backs of nude mice after treatment with intralesional injections of drugs and observed for 4 weeks. Fibroblast proliferation, scar weights, hematoxylin-eosin (HE) staining, fibroblast activity using the fibroblast-populated collagen lattice (FPCL) method, and the quantity of collagen were determined to evaluate the efficacy of the treatments. Data were analyzed using analysis of variance. All the implants were removed from animal body 4 weeks later for study. For the fibroblasts activity study, another 10 days of cell culture was done. The viability and proliferation of HSc fibroblasts in group C mice were significantly decreased at 10 days after explantation. The fibroblast numbers in the 3 groups were as follows: (A) 16.6×10⁵; (B) 1.5×10⁵; and (C) 0.4×10⁵ (P<0.05). At 4 weeks after implantation, group C showed the significantly least amount of type I collagen (A, 0.12 μg/mL; B, 0.07 μg/mL; C, 0.055 μg/mL; P<0.05). In the nonimplanted scars, the collagen in group C was 0.4 μg/mL, less than that in groups B (0.6 μg/mL) and A (1.7 μg/mL; P<0.05). Significant differences were observed in reduction of scar weight among the 3 groups (A, 85%; B, 82.3%; C, 78.6%; P<0.05). The combination therapy group, that is, group C, significant inhibition of FPCL contraction and delayed contraction of burn scar fibroblasts compared with the other groups. The FPCL contraction rate at 4 weeks in groups A, B, and C was 15.4%, 65%, and 73.4% of the original size, respectively (P<0.05). Combined intralesional injection of steroid, verapamil, and interferon exhibits significant therapeutic efficacy than does a single high dose of steroid in the treatment of hypertrophic burn scars.