Investigation of the efficacy of exosome therapy in experimentally induced acidic skin burns in rats

Introduction and aim: This study aimed to investigate the effects of adipose-derived mesenchymal stem cell–derived exosomes (ADSC-Exo) on early tissue healing in a rat model of hydrofluoric acid (HF)–induced chemical skin burns. HF burns represent a major clinical challenge due to their deep penetration, progressive necrosis, and the limited efficacy of current treatment options. Although commonly used neutralizing agents (calcium gluconate and magnesium sulfate) can reduce local toxicity, there is still no potent biotherapeutic capable of rapidly restoring tissue integrity, controlling inflammation, and limiting apoptosis. The central hypothesis of this study was that ADSC-Exo, with their anti-inflammatory, anti-apoptotic, and regenerative properties, would significantly accelerate healing in HF burns. Materials and Methods: The study was conducted at the Afyon Kocatepe University Experimental Research Unit. A total of 40 rats aged 6-8 weeks and weighing 250–350 g were randomly allocated into four groups of ten animals each: Group 1 (Sham), Group 2 (Magnesium Sulfate), Group 3 (Calcium gluconate), and Group 4 (ADSC-Exo). A standardized volume of 37% HF was applied to the dorsal skin of all animals to induce a deep chemical burn model. Anesthesia was achieved with 87 mg/kg ketamine and 13 mg/kg xylazine. Macroscopic measurements were recorded daily, and tissue biopsies were obtained on days 1, 3, and 7 for histopathological, immunohistochemical (PCNA, VEGF, TNF-α), and apoptotic assessments. Results: Baseline burn areas were similar among all groups. In the ADSC-Exo group (Group 4), burn, erythema, and necrotic tissue areas decreased more rapidly compared with the other groups, demonstrating an early and pronounced healing pattern. Histological evaluation on day 7 showed restoration of epithelial integrity, reduced inflammatory cell infiltration and hemorrhage, and a more organized hypodermal connective tissue structure in the ADSC-Exo group. Apoptosis analysis revealed significantly lower apoptotic cell counts on both days 3 and 7 in Group 4 compared with the other treatment groups. Although the calcium gluconate and magnesium sulfate groups showed improvement, they did not achieve the accelerated and comprehensive tissue recovery observed with ADSC-Exo. Conclusion: ADSC-Exo therapy markedly enhanced healing in HF-induced chemical burns by reducing inflammation, limiting apoptosis, and promoting epithelialization. These findings suggest that exosomes represent a promising and effective novel biotherapeutic option in the management of chemical burns. Keywords: Hydrofluoric acid, Chemical burn, Exosome, ADSC-Exo, Tissue healing, Apoptosis