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(1) Background: Musculoskeletal trauma from combat wounds, accidents, or surgeries is highly associated with infections and hospitalization. The current “gold standard” for such injuries when access to hospitals is limited is administering antibiotics and opioids; however, they are not ideal treatments due to their contributions to antibiotic resistance and the opioid epidemic. Electrospun chitosan acylated with lipids and loaded with hydrophobic drugs has been shown to release the therapeutics systemically and to prevent infections. (2) Methods: Electrospun chitosan membranes (ESCMs) were fabricated and acylated using decanoyl chloride. FTIR was used to confirm acylation through the presence of ester bonds and acyl chains. ESCMs were loaded with the quorum-sensing molecule cis-2-decenoic acid (C2DA) and the local anesthetic bupivacaine and then implanted in rat femurs for 3 days. Afterward, the rats were euthanized, and CFUs were measured on retrieved bone, tissue, and treatment material. (3) Conclusions: While ESCMs prevented bacterial growth on the surface of the material, controls outperformed treatment groups. This is possibly due to bupivacaine’s role in inhibiting sodium channels, which favors the production of Th2-type cytokines associated with immune response suppression. Furthermore, ESCMs provide a large surface area for bacteria to grow on and form bridges between nanofibers. 

Thermosensitive chitosan hydrogels—renewable, biocompatible materials—have many applications as injectable biomaterials for localized drug delivery in the treatment of a variety of diseases. To combat infections such as Staphylococcus aureus osteomyelitis, localized antibiotic delivery would allow for higher doses at the site of infection without the risks associated with traditional antibiotic regimens. Fosfomycin, a small antibiotic in its own class, was loaded into a chitosan hydrogel system with varied beta-glycerol phosphate (β-GP) and fosfomycin (FOS) concentrations. The purpose of this study was to elucidate the interactions between FOS and chitosan hydrogel. The Kirby Bauer assay revealed an unexpected concentration-dependent inhibition of S. aureus, with reduced efficacy at the high FOS concentration but only at the low β-GP concentration. No effect of FOS concentration was observed for the planktonic assay. Rheological testing revealed that increasing β-GP concentration increased the storage modulus while decreasing gelation temperature. NMR showed that FOS was removed from the liquid portion of the hydrogel by reaction over 12 h. SEM and FTIR confirmed gels degraded and released organophosphates over 5 days. This work provides insight into the physicochemical interactions between fosfomycin and chitosan hydrogel systems and informs selection of biomaterial components for improving infection treatment.