Development of an Experimental Ex Vivo Wound Model to Evaluate Antimicrobial Efficacy of Topical Formulations

Int J Mol Sci. 2021 May 10;22(9):5045. doi: 10.3390/ijms22095045.

Abstract

Wound infections are considered a major cause for wound-associated morbidity. There is a high demand for alternative, robust, and affordable methods that can provide relatable and reproducible results when testing topical treatments, both in research and in the pharmaceutical industry. Here we present an ex vivo wound infection model using porcine skin and a burn wounding method, allowing for the efficacy evaluation of topical antimicrobial formulations. Utilizing this model, we demonstrate the potential of topical treatments after infecting the wounds with clinically significant bacteria, P. aeruginosa and S. aureus. We show that the method is compatible with several analytical tools used to analyze infection and antimicrobial effects. Both bacterial strains successfully infected the wound surface, as well as deeper regions of the tissue. Quantification of viable bacteria on the wound surface and in the tissue, longitudinal measurements of bioluminescence, fluorescence microscopy, and scanning electron microscopy were used to confirm the effects of antibacterial treatments. Furthermore, we show that biofilms are formed on the wound surface, indicating that the demonstrated method mirrors typical in vivo infections.

Keywords: antibiotics; antimicrobial; biofilm; burn; ex vivo; wound healing; wound model.

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Infective Agents / pharmacology*
  • Biofilms / drug effects
  • Burns / drug therapy*
  • Burns / pathology
  • Disease Models, Animal
  • Drug Compounding / methods
  • Humans
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / pathology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / pathogenicity
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / pathogenicity
  • Swine
  • Wound Healing / drug effects
  • Wound Infection / drug therapy*
  • Wound Infection / microbiology
  • Wound Infection / pathology

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents