Alligator derived hyaluronic acid quells the inflammatory phase of wound healing through a dual interaction with the host and the microbiome

Introduction: Although several antimicrobials have been used in advanced wound care products such as silver and PHMB, toxicology and wound healing studies have shown that high levels of the antimicrobials can delay wound healing and are cytotoxic to keratinocytes.

Background: This study investigated the wound healing properties of a novel hyaluronic acid (HA) matrix derived from American Alligator that accelerates wound healing by quelling the inflammatory phase through the activation of NF-kB, an important transcription factor responsible for modulating inflammation.

Objective: Results demonstrated that this novel HA matrix has a dual role and is naturally bacteriostatic and fungistatic without the toxicity issues of other antimicrobials.

Methods: Cultures of bacteria (S. aureus, P. aeruginosa, S. pyogenes, E. faecalis, E. coli) were produced overnight in tryptic soy broth (TSB) at 37°C and cultures of fungi (C. albicans, C. auris) were produced in yeast extract-peptone-dextrose (YPD) overnight at 30°C. The microbe stock cultures were then diluted to 5x105 and incubated with different concentrations of HA (in pentuplicate) and incubated at their respective temperatures for 3 days. Controls included media alone, microbes alone, and streptococcal derived HA. Optical density (OD600) measurements were taken at time 0 and days 1-3.

Results: Our findings indicate that Alligator derived HA is bacteriostatic for S. aureus, S. pyogenes, E. faecalis, E. coli and fungistatic for C. albicans with limited stasis for P. aeruginosa and C. auris which are more resistant pathogens. Statistical significance of these findings (p value < 0.05) was found for all the alligator derived HA concentrations compared to the untreated microbe controls and the streptococcal derived HA.

Conclusions/Discussion: These findings indicate that the Alligator derived HA matrices have tremendous properties for jump starting chronic wound healing through a dual mechanism of modulating the inflammatory responses of both the host and microbes to provide better clinical outcomes.