Soluble chitosan derivative treats wound infections and promotes wound healing in a novel MRSA-infected porcine partial-thickness burn wound model

PLoS One. 2022 Oct 14;17(10):e0274455. doi: 10.1371/journal.pone.0274455. eCollection 2022.

Abstract

Burns are physically debilitating and potentially fatal injuries. The most common etiology of burn wound infections in the US is methicillin-resistant Staphylococcus aureus (MRSA), which is particularly recalcitrant when biofilms form. The current standard of care, silver sulfadiazine (SSD) is effective in reducing bacterial load, but less effective in improving burn wound healing. New treatments that can manage infection while simultaneously improving healing would provide a benefit in the treatment of burns. Porcine models are frequently used as a model for human wound healing but can be expensive due to the need to separate wounds to avoid cross contamination. The porcine model developed in this study offers the capability to study multiple partial thickness burn wound (PTBW) sites on a single animal with minimal crosstalk to study wound healing, infection, and inflammation. The current study evaluates a wound rinse and a wound gel formulated with a non-toxic, polycationic chitosan derivative that is hypothesized to manage infection while also promoting healing, providing a potential alternate to SSD. Studies in vitro and in this PTBW porcine model compare treatment with the chitosan derivative formulations to SSD. The wound rinse and wound gel are observed to disrupt mature MRSA biofilms in vitro and reduce the MRSA load in vivo when compared to that of the standard of care. In vivo data further show increased re-epithelialization and faster healing in burns treated with wound rinse/gel as compared to SSD. Taken together, the data demonstrate the potential of the wound rinse/gel to significantly enhance healing, promote re-epithelialization, and reduce bacterial burden in infected PTBW using an economical porcine model.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Burns* / complications
  • Burns* / drug therapy
  • Chitosan* / pharmacology
  • Chitosan* / therapeutic use
  • Humans
  • Methicillin-Resistant Staphylococcus aureus*
  • Silver Sulfadiazine / pharmacology
  • Silver Sulfadiazine / therapeutic use
  • Soft Tissue Injuries*
  • Swine
  • Wound Healing
  • Wound Infection* / drug therapy

Substances

  • Chitosan
  • Silver Sulfadiazine

Grants and funding

The work was funded by the United States Department of Defense, through the Armed Forces Institute of Regenerative Medicine (AFIRM), under Award No. W81XWH-14-2-0004, awarded to PR. Synedgen’s funding for SynePure Wound Cleanser was provided by DARPA (grant numbers N66001-14-C-4009 and N66001-12-C-4053) awarded to SB, and funding for the Catasyn Advanced Technology Wound Hydrogel was provided by the US Army (grant number W81XWH-13-C-0053 and W81XWH-16-C-0023) awarded to SB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.