Dual Modulation of Infection and Skin Recovery by Lamiaceae Hydrolate Hydrogels in S. aureus-Infected Burns

Background/Objectives: Burn wound infections caused by Staphylococcus aureus remain a major clinical challenge, leading to delayed healing and high mortality. Natural compounds derived from the Lamiaceae family possess antimicrobial and anti-inflammatory properties that may modulate wound recovery. This study aimed to evaluate the dual modulatory effects of Satureja montana and Origanum vulgare hydrolate-loaded hydrogels on modulation of infection and skin recovery in an experimental rabbit model of S. aureus-infected burns. Methods: Full-thickness (grade IIIa) thermal burns were induced in 25 male New Zealand White rabbits, followed by inoculation with S. aureus (108–109 CFU/mL). Animals were divided into five groups: sham control, burn-infection control, standard-of-care intervention, Satureja montana hydrolate intervention, and Origanum vulgare hydrolate intervention. Treatments were applied twice daily for 14 days. Bacterial load (CFU/g), biochemical markers, histological parameters, and multiplex immunohistochemical indices (Ki-67, CD68, CD163) were analyzed. Results: Both hydrolate-based formulations exhibited pronounced antibacterial effects, significantly reducing S. aureus counts by day 14 compared to untreated burns (p < 0.001). Immunohistochemical analysis revealed enhanced cell proliferation and a rapid shift from pro-inflammatory M1 (CD68+) to reparative M2 (CD163+) macrophages, indicating effective immune resolution. The hydrolate-loaded hydrogels effectively combined antimicrobial activity with tissue-regenerative and immunomodulatory effects. The S. montana formulation demonstrated superior performance, representing a promising adjunctive therapy for infected burn wounds. Conclusions: This study represents the first comparative in vivo evaluation of S. montana and O. vulgare hydrolate-loaded hydrogels in a complex S. aureus-infected burn model.