2. Academic Validation
  3. Dual-Action Topical Therapy Accelerates Healing of MRSA-Infected Burn Wounds by Targeting Infection and Inflammation

Dual-Action Topical Therapy Accelerates Healing of MRSA-Infected Burn Wounds by Targeting Infection and Inflammation

  • Adv Wound Care (New Rochelle). 2025 Dec 22. doi: 10.1177/21621918251405876.
Miaoqing Xiang 1 2,  Zongze Yao 1,  Wei Shao 3,  Mengru Chen 1,  Wenjian Tang 4,  Dandan Liu 2,  Jing Zhang 2 3
Affiliations

Affiliations

  • 1 School of Medicine, Anhui University of Science and Technology, Huainan, China.
  • 2 Anhui Province Key Laboratory of Occupational Health, Anhui No. 2 Provincial People's Hospital, Hefei, China.
  • 3 Joint Research Center for Occupational Medicine and Health of IHM, Anhui University of Science and Technology, Huainan, China.
  • 4 School of Pharmacy, Anhui Medical University, Hefei, China.
PMID: 41449962 DOI: 10.1177/21621918251405876
Abstract

Objective: Burn injuries affect over 11 million people annually, and methicillin-resistant Staphylococcus aureus (MRSA) Infection significantly delays healing by sustaining inflammation and promoting scarring. This study evaluated N-benzyl benzenamine 4k-a novel dual-action compound with Antibacterial and anti-inflammatory properties-in a murine model of MRSA-infected burn wounds. Approach: Skin safety of 4k was assessed through acute toxicity, sensitization, and irritation tests in BALB/c mice. A full-thickness burn model infected with MRSA2858 (1 × 108 CFU/mL) was treated topically with 4k, vancomycin (VAN), or vaseline. Outcomes included wound closure, Bacterial load, histology, Collagen organization, macrophage polarization markers (CD86/inducible nitric oxide synthase [iNOS] for M1; CD206/vascular endothelial growth factor [VEGF] for M2), cytokine levels, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway proteins. Results: 4k demonstrated excellent dermal tolerability with no toxicity or irritation. Topical 4k reduced MRSA colonization and accelerated wound closure (residual wound area at day 15: 4k = 8.4 ± 2.2%, VAN = 17.8 ± 3.5%). Histology revealed organized Collagen deposition and minimal scarring in the 4k group (scar score: 2.33 ± 0.58 vs. 13.33 ± 0.58 for vaseline). Mechanistically, 4k suppressed NF-κB activation, downregulated M1 markers (CD86, iNOS, tumor necrosis factor-alpha, and interleukin [IL]-6), and upregulated M2 markers (CD206, VEGF, transforming growth factor-beta 1, and IL-10), promoting a prohealing immune environment. Innovation: This study introduces a dual-action topical therapy that combines potent Antibacterial activity with immunomodulation, offering a promising strategy to overcome Antibiotic resistance and improve burn wound outcomes. Conclusions: N-benzyl benzenamine 4k effectively eradicates MRSA, accelerates wound healing, and minimizes scarring through NF-κB inhibition and macrophage polarization, supporting its potential as a next-generation burn care agent.

Keywords

MRSA; NF-κB pathway; burn wound healing; dual-action therapy; inflammation; macrophage polarization.

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