Comparative Evaluation of Single and Combination Pharmacologic and Device-Based Anti-scar Therapies in a Murine Linear Wound Model.

Abstract

BACKGROUND: Scarring, a form of tissue fibrosis, is an unavoidable outcome of wound healing and can lead to cosmetic, functional, and psychological burdens. While both surgical and non-surgical treatments are available, non-invasive topical therapies are generally more acceptable to patients and easier to maintain over the long-term. Despite the availability of various anti-scar products targeting inflammation, hydration, and mechanical tension, there is a lack of comparative data on their individual and combined efficacy. Therefore, evidence-based guidance is needed to optimize scar prevention strategies. METHODS: Full-thickness linear wounds were established on the dorsal skin of C57BL/6 mice. After re-epithelialization, mice were randomly assigned to receive one of eleven single treatments or one of four combination regimens over a 14-day period. Scar width measurements, histological assessments, and immunohistochemical analyses targeting TGF-β1, α-SMA, and collagen type I and type III were conducted on postoperative day 28. RESULTS: All single therapies reduced scar width compared to the control, with Centella asiatica-chitosan and tension reducer groups showing the most notable outcomes. Combination therapies, particularly triple-combination strategies (ointment + silicone-based product + mechanical interventions), achieved superior scar inhibition and more favorable molecular profiles, including reduced TGF-β1, α-SMA, collagen type I expression, and elevated collagen type III levels. These benefits appeared to reflect complementary and possibly synergistic mechanisms across pharmacologic, silicone-based, and mechanical pathways, rather than simple additivity. CONCLUSION: Both single and combination interventions exhibited measurable anti-scar effects, but triple-combination strategies-especially those integrating biochemical and biomechanical modulation-produced the most significant improvements. These findings support the clinical adoption of mechanism-guided combination therapies for optimized scar prevention and treatment. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .