Thesis Defense Announcement

Herff College of Engineering announces the Final Thesis Defense of

Leslie Pace

for the Degree of Master of Science

March 21, 2019 at 1:00 PM in Engineering Science Building, Room 335

Advisor: Amber Jennings

Development and Evaluation of an Injectable Chitosan-Mannitol Paste as an Antimicrobial Delivery System for the Inhibition and Eradication of Biofilm

ABSTRACT: Osteomyelitis is an infection of the bone, which is commonly caused by Staphylococcus aureus. Bacterial attachment to a surface is also known as biofilm and is a major concern in the realm of orthopedics, specifically periprosthetic joint replacements. Implanted materials can increase the risk of osteomyelitis, leading S. aureus to develop a complex biofilm not only on the materials but also in bone and soft tissue surrounding the joint. A biofilm is intrinsically less susceptible to antibiotic therapy than free-floating planktonic microorganisms due to decreased metabolic rates and the dormant persister cell phenotype. Mannitol, a sugar polyol has been shown to activate persister cell metabolism, priming microorganisms for the uptake of antibiotics and subsequent eradication. Blends of mannitol and chitosan combine the anti-biofilm properties of mannitol with the drug-delivering capability of chitosan. The goal of this project is to evaluate the chitosan/mannitol blends with poly(ethylene glycol) as a biocompatible, injectable local antibiotic delivery system capable of degrading within the body, eradicating established biofilm in vitro, and preventing osteomyelitis in vivo. Results have indicated the mannitol/chitosan blend is capable of eluting antibiotics for up to 7 days, antimicrobial activity up to 7 days, and antimicrobial activity against established biofilm with and without antibiotics in several preclinical models of infection, including a rabbit osteomyelitis model. Qualitative results indicate the mannitol/chitosan blends are more adhesive than previous injectable pastes and form a viscous complex believed to be from the interaction of the mannitol hydroxyl groups with positively charged amino groups of chitosan. Clinically, this paste could serve as a biodegradable local antibiotic delivery system at the time of surgery to prevent infection, during periprosthetic joint revision surgeries, or complex musculoskeletal trauma to prevent and treat an infection.