Biofilm Impaired Wound Healing

MISSION

Our focus on biofilms is not restricted to dental disease, as microbial colonization occurs in both acute and chronic wounds. Combat wounds, in particular, represent additional challenges due to: (a) heavy contamination of dirt, organic debris and clothing; (b) high-energy projectile wounding causes significant devitalized tissue, hematoma, and tissue ischemia; and (c) delays in casualty evacuation.

In addition to primary wound infections, combat casualties hospitalized in tertiary care medical treatment facilities are at high risk for nosocomial infections. These infections develop days after injury and are largely due to multi-drug resistant gram-negative organisms including Acinetobacter, Pseudomonas, Enterobacter, and Klebsiella species. The persistence of recurrent infections in combat wounds defies current treatment modalities and results in significant morbidity to service members (SM).

In an effort to understand biofilm-infected wounds, we study bacteria themselves and the biofilms they create, utilizing several in vitro and in vivo models. Our in vitro models allow us to study the growth, development and control of oral biofilms, and determination of the efficacy of antimicrobial drugs.

The objective of our research is to elucidate the interactions of multiple organisms, providing insight into the factors used in the establishment of a polymicrobial biofilm. Our ongoing collaboration with Northwestern University has resulted in the development of an in vivo, rabbit ear, biofilm-infected wound model, which is one of the most accurate representation of biofilm-infected human chronic wounds to date. Through the use of this model, we have learned that conventional wound care is not effective in mitigating biofilms in wounds.

Due to antimicrobial resistance, it is necessary to identify novel agents to replace the current array of antimicrobials used. We are developing anti-microbial therapeutics, such as KSL-W peptide, formulated in hydrogels or polymers for topical application, as well as other peptides through academic and industrial collaborations.

Future research in this area will utilize a high throughput screen method, whereby, biofilms are treated by various compounds, from a defined chemical library, to identify compounds that are able to significantly disrupt biofilm persistence; the most significant compounds that will then be tested in the biofilm-infected wound animal model.

This data will provide the groundwork for further understanding and exploiting of polymicrobial interactions that contribute to chronic infection and appropriate drugs to treat them.