Enhanced Susceptibility to Infections in a Diabetic Wound Healing Model

Abstract

Background: Wound infection is a common complication in diabetic patients. The progressive spread of infections and development of drug-resistant strains underline the need for further insights into bacterial behavior in the host in order to develop new therapeutic strategies. The aim of our study was to develop a large animal model suitable for monitoring the development and effect of bacterial infections in diabetic wounds. Method: Fourteen excisional wounds were created on the dorsum of diabetic and non-diabetic Yorkshire pigs and sealed with polyurethane chambers. Wounds were either inoculated with \(2 \times 10^8\) Colony-Forming Units (CFU) of Staphylococcus aureus or injected with 0.9% sterile saline. Blood glucose was monitored daily, and wound fluid was collected for bacterial quantification and measurement of glucose concentration. Tissue biopsies for microbiological and histological analysis were performed at days 4, 8, and 12. Wounds were assessed for reepithelialization and wound contraction. Results: Diabetic wounds showed a sustained significant infection (>\(10^5\) CFU/g tissue) compared to non-diabetic wounds (p < 0.05) over the whole time course of the experiment. S. aureus-inoculated diabetic wounds showed tissue infection with up to \(8 \times 10^7\) CFU/g wound tissue. Non-diabetic wounds showed high bacterial counts at day 4 followed by a decrease and no apparent infection at day 12. Epidermal healing in S. aureus-inoculated diabetic wounds showed a significant delay compared with non-inoculated diabetic wounds (59% versus 84%; p < 0.05) and were highly significant compared with healing in non-diabetic wounds (97%; p < 0.001). Conclusion: Diabetic wounds developed significantly more sustained infection than non-diabetic wounds. S. aureus inoculation leads to invasive infection and significant wound healing delay and promotes invasive co-infection with endogenous bacteria. This novel wound healing model provides the opportunity to closely assess infections during diabetic wound healing and to monitor the effect of therapeutical agents in vivo.