Presentation Title

Optimization of a Molecularly-Imprinted Material for Treatment of Biofilm Infections

Project Collaborators

Amber Doiron (PI), Alicia Tanneberger, Ian Cochrane, Danielle Sedler, Susanna Li

Abstract

While advanced medical care has improved the survival rate of burn patients to date, there is still a significant need to address the 75% of all deaths that occur due to sepsis or other burn wound infections that are commonly seen in severely burned patients. Surface-associated bacterial aggregates, or biofilms, can form in human burn wounds within 10-24h of thermal injury. Due to changes in phenotype, mature biofilm bacteria are up to 1000-fold less susceptible to various antimicrobial agents than their free-floating (planktonic) counterparts, rendering current treatments ineffective. Recent work demonstrates that Pseudomonas aeruginosa and Staphylococcus aureus biofilms require the metabolite pyruvate for both growth and maintenance, with enzymatic depletion of pyruvate by pyruvate dehydrogenase (PDH) resulting in impaired biofilm formation and enhanced biofilm disruption and killing. However, the PDH quickly loses its activity due to the susceptibility of enzymes to pH changes, temperature fluctuations during storage or treatment, and proteases present in vivo. In order to circumvent these drawbacks, we have developed a molecularly-imprinted hydrogel material capable of binding pyruvate as an initial step towards the long-term goal of developing a wound dressing that disrupts biofilms by removing pyruvate, thereby preventing and eliminating biofilm infections from wounds. Preliminary binding experiments have shown enhanced pyruvate uptake in solution by molecularly-imprinted gels compared to their nonmolecularly-imprinted counterparts. Current work is aimed at quantifying binding selectivity in a simplified wound exudate solution with pyruvate, lactate, and glucose followed by optimization of formulation parameters in order to maximize pyruvate selectivity and binding efficiency. Additionally, characterization of the mechanical and surface properties of the gel are being investigated to determine its feasibility as a wound dressing in clinical applications. Future work will address the biocompatibility of the material and explore other polymer-based avenues for synthesis of pyruvate binding materials.

Primary Faculty Mentor Name

Amber Doiron

Status

Undergraduate

Student College

College of Engineering and Mathematical Sciences

Program/Major

Biomedical Engineering

Primary Research Category

Engineering & Physical Sciences

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Optimization of a Molecularly-Imprinted Material for Treatment of Biofilm Infections

While advanced medical care has improved the survival rate of burn patients to date, there is still a significant need to address the 75% of all deaths that occur due to sepsis or other burn wound infections that are commonly seen in severely burned patients. Surface-associated bacterial aggregates, or biofilms, can form in human burn wounds within 10-24h of thermal injury. Due to changes in phenotype, mature biofilm bacteria are up to 1000-fold less susceptible to various antimicrobial agents than their free-floating (planktonic) counterparts, rendering current treatments ineffective. Recent work demonstrates that Pseudomonas aeruginosa and Staphylococcus aureus biofilms require the metabolite pyruvate for both growth and maintenance, with enzymatic depletion of pyruvate by pyruvate dehydrogenase (PDH) resulting in impaired biofilm formation and enhanced biofilm disruption and killing. However, the PDH quickly loses its activity due to the susceptibility of enzymes to pH changes, temperature fluctuations during storage or treatment, and proteases present in vivo. In order to circumvent these drawbacks, we have developed a molecularly-imprinted hydrogel material capable of binding pyruvate as an initial step towards the long-term goal of developing a wound dressing that disrupts biofilms by removing pyruvate, thereby preventing and eliminating biofilm infections from wounds. Preliminary binding experiments have shown enhanced pyruvate uptake in solution by molecularly-imprinted gels compared to their nonmolecularly-imprinted counterparts. Current work is aimed at quantifying binding selectivity in a simplified wound exudate solution with pyruvate, lactate, and glucose followed by optimization of formulation parameters in order to maximize pyruvate selectivity and binding efficiency. Additionally, characterization of the mechanical and surface properties of the gel are being investigated to determine its feasibility as a wound dressing in clinical applications. Future work will address the biocompatibility of the material and explore other polymer-based avenues for synthesis of pyruvate binding materials.