Background Open orthopaedic wounds are ideal sites for infection. Preventing infection in these wounds is critical for reducing patient morbidity and mortality, controlling antimicrobial resistance and lowering the cost of treatment. Localized drug delivery has the potential to overcome the challenges associated with traditional systemic dosing. A degradable, biocompatible polymer sponge (chitosan) that can be loaded with clinician-selected antibiotics at the point of care would provide the patient and clinician with a desirable, adjunctive preventive modality. Questions/purposes We asked (1) if an adaptable, porous chitosan matrix could absorb and elute antibiotics for 72 hours for potential use as an adjunctive therapy to débri-dement and lavage; and (2) if the sponges could elute levels of antibiotic that would inhibit growth of Staphylococcus aureus and Pseudomonas aeruginosa? Methods We fabricated a degradable chitosan sponge that can be loaded with antibiotics during a 60-second hydration in drug-containing solution. In vitro evaluation determined amikacin and vancomycin release from chitosan sponges at six time points. Activity tests were used to assess the release of inhibitory levels of amikacin and vancomycin. Results Amikacin concentration was 881.5 lg/mL after 1 hour with a gradual decline to 13.9 lg/mL after 72 hours. Vancomycin concentration was 1007.4 lg/mL after 1 hour with a decrease to 48.1 lg/mL after 72 hours. Zone of inhibition tests were used to verify inhibitory levels of drug release from chitosan sponges. A turbidity assay testing activity of released amikacin and vancomycin indicated inhibitory levels of elution from the chitosan sponge. Clinical Relevance Chitosan sponges may provide a potential local drug delivery device for preventing musculoskeletal infections.

Local antibiotic delivery is an emerging area of study designed to provide alternative methods of treatment to clinicians for compromised wound sites where avascular zones can prevent the delivery of antibiotics to the infected tissue. Antibiotic-loaded bone cement is the gold standard for drug-eluting local delivery devices but is not ideal because it requires a removal surgery. Chitosan is a biocompatible, biodegradable polymer that has been used in several different drug delivery applications. We evaluated chitosan as a potential localized drug delivery device. We specifically determined if chitosan could elute antibiotics in an active form that would be efficacious in inhibiting S. aureus growth. Elution of amikacin was 24.67 ± 2.35 lg/mL (85.68%) after 1 hour with a final cumulative release of 27.31 ± 2.86 lg/mL (96.23%) after 72 hours. Elution of daptomycin was 10.17 ± 3.83 lg/mL after 1 hour (31.61% release) and 28.72 ± 6.80 lg/mL after 72 hours (88.55%). The data from the elution study suggested effective release of amikacin and daptomycin. The activity studies indicated the eluants inhibited the growth of S. aureus. Incorporating antibiotics in chitosan could provide alternative methods of treating musculoskeletal infections.

The chitosan sponges are effective delivering the antibiotic and reducing the bacteria within the wounds.

Oral nonsteroidal antiinfl ammatory drugs (NSAIDs) are prescribed for heterotopic ossifi cation prophylaxis following at-risk injuries and procedures. We hypothesized that NSAIDs may be delivered locally in a wound for heterotopic ossifi cation prophylaxis. In in vitro work, we cultured osteoblasts with three commercially available NSAIDs and then measured cell viability and DNA content. Indomethacin caused a 50% decrease in DNA at the lowest dose (0.0001 mM) and the most potent decrease in cell viability (<10% of control at 0.0005 mM). Ketorolac and ibuprofen required 10 times the dose to achieve a comparable decrease (<20% of control at 0.005 mM). In an animal study, 20 rats per treatment group received a full-thickness wound dressed with either saline-moistened gauze, salinemoistened chitosan sponge, or chitosan sponge loaded with indomethacin. After 28 days, we examined the tissue for healing. Wounds exposed to indomethacin loaded sponges demonstrated fewer infl ammatory cells. All 20 rats in the indomethacin group had complete epithelial coverage at 28 days. Eighteen (90%) wounds in the saline-chitosan group and 11 (55%) wounds in the saline-gauze group were healed. Locally delivered NSAIDs may be useful for heterotopic ossifi cation prophylaxis due to effects on osteoblast viability and lack of negative effects on wound healing. Clin Trans Sci 2015; Volume 8: 591-593