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

<b>Background/Objectives:</b> Burn wound infections caused by <i>Staphylococcus aureus</i> remain a major clinical challenge, leading to delayed healing and high mortality. Natural compounds derived from the <i>Lamiaceae</i> family possess antimicrobial and anti-inflammatory properties that may modulate wound recovery. This study aimed to evaluate the dual modulatory effects of <i>Satureja montana</i> and <i>Origanum vulgare</i> hydrolate-loaded hydrogels on modulation of infection and skin recovery in an experimental rabbit model of <i>S. aureus</i>-infected burns. <b>Methods:</b> Full-thickness (grade IIIa) thermal burns were induced in 25 male New Zealand White rabbits, followed by inoculation with <i>S. aureus</i> (10⁸-10⁹ CFU/mL). Animals were divided into five groups: sham control, burn-infection control, standard-of-care intervention, <i>Satureja montana</i> hydrolate intervention, and <i>Origanum vulgare</i> 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. <b>Results:</b> Both hydrolate-based formulations exhibited pronounced antibacterial effects, significantly reducing <i>S. aureus</i> counts by day 14 compared to untreated burns (<i>p</i> < 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 <i>S. montana</i> formulation demonstrated superior performance, representing a promising adjunctive therapy for infected burn wounds. <b>Conclusions:</b> This study represents the first comparative in vivo evaluation of <i>S. montana</i> and <i>O. vulgare</i> hydrolate-loaded hydrogels in a complex <i>S. aureus</i>-infected burn model.