119 A Nitric Oxide Releasing Bio-active Wound Dressing for Burn Wound Infection Treatment

Abstract

Abstract Introduction The future of multi-domain battlefield operation requires wound dressings to prevent infection at the point of injury. Majority of antimicrobial agents only target wound infection while other healing events are left to their natural fates. Nitric oxide (NO) acts against both gram-positive and -negative bacteria and has the potential to positively affect wound healing. In this study we have developed a novel wound dressing integrated with a NO donor - S-nitroso- glutathione (GSNO) in a hybrid formulation of alginate and poly(vinyl alcohol) (PVA) to prevent/treat burn wound infection. Methods The NO releasing wound dressing was fabricated using PVA, alginate, and glycerol, crosslinked with CaCl2 incorporating GSNO. Thereafter, release kinetics were measured up to 4 days. The antibacterial efficacy was determined against both P. aeruginosa and S. aureus. Then the biocompatibility of the NO wound dressing was assessed using in vitro fibroblast proliferation and wound healing assay. Finally, the efficacy of the wound dressing was assessed in vivo using a 3-cm diameter porcine burn wound infection model. Results The Alginate-PVA-GSNO dressing showed a desired physiological level NO flux of 4.42 × 10-10 mol cm-2 min-1 for 72 hours. Alginate−PVA−GSNO dressings showed ~3 log reduction in S. aureus and ~2 log reduction in P. aeruginosa CFU/mg when compared to control. The NO-releasing dressing improved fibroblast proliferation and migration resulting in complete closure of the wound within 48 h in vitro. The safety and efficacy of NO-releasing dressing were successfully established in the both P. aeruginosa and S. aureus infected porcine burn wounds. Histological assessments are carried out to determine the effect of NO-releasing dressing on overall healing process. Conclusions This study shows Alginate−PVA-GSNO wound dressing provides antimicrobial and wound healing properties in vitro. Preliminary in vivo wound healing studies established the safety and efficacy profile of NO-releasing dressing to treat burn wounds. Applicability of Research to Practice An easy to apply, field deployable and effective antimicrobial wound dressing is still a major requisite for combat burn wounds. NO delivering alginate-PVA based wound dressing may be an ideal candidate to inhibit infection as well as promote the wound healing process.