Comparative efficacy of resorbable fiber wraps loaded with gentamicin sulfate or gallium maltolate in the treatment of osteomyelitis
Autor: | Michael Whitely, Joshua McCune, Annika Balakrishnan, Ziyang Lan, Taneidra W. Buie, Joseph C. Wenke, Elizabeth Cosgriff-Hernandez, Anupriya Jose |
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Rok vydání: | 2021 |
Předmět: |
Male
Staphylococcus aureus Materials science medicine.drug_class 0206 medical engineering Antibiotics Biomedical Engineering 02 engineering and technology Bone healing Pharmacology Cell Line Rats Sprague-Dawley Biomaterials Mice chemistry.chemical_compound Organometallic Compounds medicine Animals Osteomyelitis Bone Cements technology industry and agriculture Metals and Alloys Staphylococcal Infections 021001 nanoscience & nanotechnology medicine.disease Antimicrobial 020601 biomedical engineering Controlled release Rats Gallium maltolate Gentamicin Sulfate chemistry Pyrones Ceramics and Composites Gentamicin Gentamicins 0210 nano-technology medicine.drug |
Zdroj: | Journal of Biomedical Materials Research Part A. 109:2255-2268 |
ISSN: | 1552-4965 1549-3296 |
DOI: | 10.1002/jbm.a.37210 |
Popis: | The high incidence of osteomyelitis associated with critical-sized bone defects raises clinical challenges in fracture healing. Clinical use of antibiotic-loaded bone cement as an adjunct therapy is limited by incompatibility with many antimicrobials, sub-optimal release kinetics, and requirement of surgical removal. Furthermore, overuse of antibiotics can lead to bacterial modifications that increase efflux, decrease binding, or cause inactivation of the antibiotics. Herein, we compared the efficacy of gallium maltolate, a new metal-based antimicrobial, to gentamicin sulfate released from electrospun poly(lactic-co-glycolic) acid (PLGA) wraps in the treatment of osteomyelitis. In vitro evaluation demonstrated sustained release of each antimicrobial up to 14 days. A Kirby Bauer assay indicated that the gentamicin sulfate-loaded wrap inhibited the growth of osteomyelitis-derived isolates, comparable to the gentamicin sulfate powder control. In contrast, the gallium maltolate-loaded wrap did not inhibit bacteria growth. Subsequent microdilution assays indicated a lower than expected sensitivity of the osteomyelitis strain to the gallium maltolate with release concentrations below the threshold for bactericidal activity. A comparison of the selectivity indices indicated that gentamicin sulfate was less toxic and more efficacious than gallium maltolate. A pilot study in a contaminated femoral defect model confirmed that the sustained release of gentamicin sulfate from the electrospun wrap resulted in bacteria density reduction on the surrounding bone, muscle, and hardware below the threshold that impedes healing. Overall, these findings demonstrate the efficacy of a resorbable, antimicrobial wrap that can be used as an adjunct or stand-alone therapy for controlled release of antimicrobials in the treatment of osteomyelitis. |
Databáze: | OpenAIRE |
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