Staphylococcal biofilms impair wound healing by delaying reepithelialization in a murine cutaneous wound model

TLDR

Bacterial biofilms are ubiquitous, studied in various in vivo models, and are increasingly recognized in chronic wounds such as pressure sores, diabetic foot ulcers, and venous stasis ulcers. The study introduces a novel murine cutaneous wound model that directly shows delayed reepithelialization caused by bacterial biofilms. Biofilms were established by inoculating Staphylococcus aureus or Staphylococcus epidermidis into splinted punch wounds on C57Bl6/J mice. Biofilm presence significantly delayed wound reepithelialization, an effect dependent on biofilm formation as shown by biofilm‑inhibiting peptides and biofilm‑deficient mutants, providing the first direct evidence of biofilms impairing cutaneous wound healing.

Abstract

ABSTRACT Bacterial biofilms have gained increasing visibility in recent years as a ubiquitous form of survival for microorganisms in myriad environments. A number of in vivo models exist for the study of biofilms in the setting of medically relevant implanted foreign bodies. Growing evidence has demonstrated the presence of bacterial biofilms in the setting of a number of chronic wound states including pressure sores, diabetic foot ulcers, and venous stasis ulcers. Here we present a novel murine cutaneous wound system that directly demonstrates delayed reepithelialization caused by the presence of a bacterial biofilm. We established biofilms using either Staphylococcus aureus or Staphylococcus epidermidis in splinted cutaneous punch wounds created on the backs of normal C57Bl6/J mice. Wound reepithelialization was significantly delayed by bacterial biofilms. This effect was specifically dependent on the ability of the bacteria to form biofilms as demonstrated by exogenous administration of biofilm inhibiting peptides and the use of mutant Staphylococcus spp. deficient in biofilm formation. This represents the first direct evidence for the effect of bacterial biofilms on cutaneous wound healing.