Comparison of rat hypertrophic scar models: Caudal tension model with superior pathological consistency

Abstract

Background

Hypertrophic scars (HS) are a common fibrotic disorder in skin wound healing, characterized by excessive fibroblast proliferation and abnormal collagen deposition, with an incidence reaching 40%–70% in burn patients. Current treatments (e.g., corticosteroid injections) face challenges such as high recurrence rates and significant adverse effects, highlighting the urgent need for reliable animal models to investigate pathogenesis and develop novel therapies.

Methods

Forty-eight male Sprague–Dawley (SD) rats were used to systematically compare modeling efficacy across auricular (3.5 mm corneal trephine), dorsal (linear incision/tension/full-thickness excision), and caudal (linear incision/tension) sites. Each subgroup contained 12 rats (n = 12/group). Scar formation was evaluated over 60 days via macroscopic observation, Vancouver Scar Scale (VSS) scoring, H&E/Masson staining (fibroblast density/collagen deposition), and immunofluorescence α-smooth muscle actin (α-SMA), transforming growth factor beta (TGF-β), type I collagen/type III collagen (COL I/III).

Results

The caudal tension group demonstrated optimal outcomes, with scar thickness (0.394 ± 0.006 mm), fibroblast density (1079 ± 118 cells/mm²), and collagen deposition (90.6% ± 2.4%) significantly higher than other groups (***p < 0.001), alongside sustained upregulation of α-SMA and TGF-β. The auricular site was excluded due to rapid self-healing.

Conclusion

The tension method on the tail is a simple, stable, and clinically relevant HS model, effectively replicating human pathological features and providing an ideal platform for disease mechanism research and drug screening.