| Musculoskeletal wound infection as a result of traumatic injury is a life threatening condition that occurs in both military and civilian environments. Standard treatment is lifesaving first aid to stabilize a patient's vital signs, followed by surgical intervention including debridement, irrigation, and systemic antibiotic therapy. After surgical intervention, if no infection is evident, hard tissues are stabilized and the wound is closed. Adjunctive therapy via local drug delivery of antibiotics is beneficial in musculoskeletal wounds to prevent infection establishment where the penetration of antibiotics is prohibited by compromised vasculature. Local antibiotic delivery, using the biomaterial chitosan, has the potential to provide a biodegradable and non-cytotoxic solution compared to other, current drug delivery devices. A newly developed, mildly acidic, chitosan paste will function as a biodegradable, non-toxic, as well as injectable and adhesive, antibiotic delivery device for infection prevention in musculoskeletal wounds. The objective of the work presented herein, was to evaluate the chitosan paste device's characteristics and functional abilities in vitro and in vivo. The in vitro analysis demonstrated the chitosan paste's ability to be applied by injection from taper-tip syringe and be adhesive in clinically relevant situations. The paste was able to incorporate and release antibiotics, while degrading without a prolonged cytotoxic effect. In vivo analysis in a rat, intramuscular, biocompatibility model indicated that additional chitosan paste formulation, specifically the acidic to neutralized product ratio, is needed to improve biocompatibility, while an infection prevention, mouse biofilm model demonstrated the device was effective at reducing bacterial load. These results led to the conclusion that, with further study and optimization, the chitosan paste shows potential as an adjunctive, local, infection prevention therapy to standard surgical debridement, irrigation and lavage treatment for bacterial contaminated musculoskeletal wounds. |
