Numerous events can lead to bacterial infections of the skeletal system, including musculoskeletal injuries, especially open fractures and orthopaedic procedures, such as implants or bone grafts. Open fractures (associated with overlying skin and soft tissue injuries) often result in exposure of injured tissue and fractured bone to contaminating microorganisms, leading to infection more often than closed fractures. Surgical procedures, especially those involving implants or bone grafts, expose these same tissues to contamination. Bacterial contamination is often further complicated by compromised local vasculature and formation of bacterial biofilm in wound tissues and in the devices used for stabilization and post-surgical repair. All of these factors can contribute to severe negative treatment outcomes, including increased morbidity, extended length of treatment, and higher cost. Degradable and non-degradable local antibiotic delivery systems are often used to supplement traditional regimens of systemic antibiotic administration and surgical debridement. While these systems can achieve high concentrations of antibiotics at the injury site, each has associated problems such as poor degradability, incomplete site coverage, or inadequate release profiles. To address the critical need for improved methods of targeted antimicrobial delivery, we will build on our previous research to develop and test an injectable paste with sponge aggregates, using a degradable composite material derived from the natural biomaterial chitosan. This tunable composite paste will be engineered to deliver point-of-care, clinician-selected antibiotics and to provide full coverage in complex wound areas and irregularly shaped biomaterials, e.g., fixation devices. We hypothesize that the injectable, antibiotic-loaded chitosan composite paste will locally deliver levels of antibiotics that effectively eliminate contaminating microorganisms and prevent biofilm formation in traumatic wounds. After in vitro evaluations of elution, degradation, bactericidal, and anti-biofilm and physical properties of the paste and a preliminary animal model in vivo biocompatibility study, two established infected animal models with increasing complexity will be used to functionally assess the paste composite with antibiotics (selected for Gram + and Gram - coverage. The new composite paste system will also be compared to the traditional local delivery systems, polymethyl-methacrylate beads and calcium sulfate. We will tailor our tunable and degradable composite paste delivery system to meet clinical needs for preventing infections in complex musculoskeletal trauma.

Public Health Relevance

Infections of musculoskeletal surgical sites and surgeries for traumatic bone injuries are increasing and negatively impacting treatment outcomes and costs. Current methods of infection prevention and treatment through systemic and/or local antimicrobial delivery are not optimally effective in terms of either clinical outcomes or costs. W will investigate and test a tunable composite for local delivery to the infected wound site to potentially prevent contamination, enhance treatment outcomes and quality of life, and reduce health care costs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR066050-04
Application #
9418581
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Washabaugh, Charles H
Project Start
2015-03-10
Project End
2019-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Memphis
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
055688857
City
Memphis
State
TN
Country
United States
Zip Code
38152
Berretta, Joel M; Jennings, Jessica A; Courtney, Harry S et al. (2017) Blended Chitosan Paste for Infection Prevention: Preliminary and Preclinical Evaluations. Clin Orthop Relat Res 475:1857-1870
Rhodes, Cheyenne S; Alexander, Christopher M; Berretta, Joel M et al. (2017) Evaluation of a chitosan-polyethylene glycol paste as a local antibiotic delivery device. World J Orthop 8:130-141
Smith, J Keaton; Bumgardner, Joel D; Courtney, Harry S et al. (2010) Antibiotic-loaded chitosan film for infection prevention: A preliminary in vitro characterization. J Biomed Mater Res B Appl Biomater 94:203-11