The influence of the antimicrobial topical ointment, Blastx, on the wound healing process in uninfected and Staphylococcus aureus infected wounds

Date

2021-05

Journal Title

Journal ISSN

Volume Title

Publisher

Abstract

Chronic wounds, which include pressure ulcers and diabetic foot ulcers, affect approximately 6.5 million people with high annual treatment. Staphylococcus aureus, one of the bacterial pathogens commonly isolated from infected chronic wounds, prevents or slows the wound healing process. If not interrupted, wound healing occurs through four overlapping stages: hemostasis, inflammation, proliferation, and remodeling. Within each stage, there are a variety of interactions that involve immune and non-immune host cells as well as cytokines/chemokines. Topical antimicrobials, which reduce the bacterial bioburden within the wound, may either benefit, have no effect, or produce an adverse effect on the wound healing process. Previously, we showed that BlastX wound gel eliminated the S. aureus bioburden from an infected wound. However, the effect of BlastX wound gel on the wound healing process in an uninfected and in an infected wound is not known. BlastX wound gel may promote the wound healing process by influencing the host immune response. Using the murine model of excision wounds, we assessed the influence of BlastX wound gel on the wound healing process in an uninfected and in a S. aureus infected wounds. For the uninfected studies, a 1.5 × 1.5-cm full thickness excision wound was generated on the dorsum of each mouse and the injured/uninfected mice were randomized into three groups (3-4 mice/group/time point); untreated (control), polyethylene glycol treated (PEG; vehicle control), and BlastX wound gel treated. For the infection studies, the murine model of excision wounds was utilized, and each wound was infected with S. aureus for 8 hours. At 8 hours post infection, the injured mice were randomized and treated similar to the uninfected studies. The mice were examined at 1, 3, and 7 days post-treatment (Ds-PT). At each time point, the wound closure rate was assessed. In addition, mice were euthanized; the wounded tissues were excised and examined microscopically for: tissue granulation, neovascularization, re-epithelization rate, and hair follicle formation. Furthermore, we determined the level of neutrophils, M2-macrophages, M1-macrophages, and cytokines/chemokines within the wounds. The wound closure rate was similar among the three groups in uninfected and infected experiments. In the uninfected wounds and compared to the untreated and PEG treated groups, BlastX wound gel treated wounds had several unique features; 1) BlastX wound gel treated wounds showed blood clot formation on D1-PT; 2) By D3-PT, BlastX wound gel treated wounds had the presence of neovascularization, organized scab development, M2 macrophages, and a significantly higher level of re-epithelization; 3) BlastX wound gel treatment reduced the levels of pro-inflammatory cytokines IL-1β, IL-6, CCL3, and CXCL1 within the wound; 4) On D7-PT, with the exception of an increased level of IL-6, BlastX wound gel treated wounds had no other significant changes. With respect to the infected wounds, we did not observe major changes between the uninfected/BlastX wound gel treated wounds and the infected/BlastX wound gel treated wounds with the exception of; 1) an increased number of M1 macrophages on D1-PT in the infected/BlastX wound gel treated wounds; 2) At D3-PT, the infected/BlastX wound gel wound showed unorganized scab formation and no sign of neovascularization or granulation within the wound; 3) The rate of re-epithelization and hair follicle formation was decreased; 4) The number of M2 macrophages was decreased within the infected/BlastX wound gel treated wounds; 5) On D7-PT, the infected/BlastX wound gel treated wounds had no neovascularization and contained M1 macrophages; 6) On 1, 3, and 7 Ds-PT, BlastX wound gel eliminated S. aureus from the wound bed. These results suggest that: a) BlastX wound gel does not interfere with the wound healing process and may enhance the healing process on D3-PT in an uninfected wound, b) BlastX wound gel does not interfere with the wound healing process in an S. aureus infected wound, and c) any changes observed between the uninfected/BlastX wound gel and the infected/BlastX wound gel treated groups are likely due to the S. aureus infection prior to BlastX wound gel treatments.

Description

Keywords

Wound Healing, Chronic Wounds, Topical Antimicrobial, Staphylococcus Aureus

Citation