Comparative efficacy of resorbable fiber wraps loaded with gentamicin sulfate or gallium maltolate in the treatment of osteomyelitis

Abstract

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.

Choosing the right animal model for osteomyelitis research: Considerations and challenges

“…2 a). Chen et al [ 86 , [116] , [117] , [118] ] developed a rat model with 6-mm femur segmental defect and stabilization with a poly-acetyl plate and six threaded Kirschner wires (K-wire), which has been frequently adopted by other researchers [ [87] , [88] , [89] , [119] , [120] , [121] , [122] , [123] , [124] , [125] , [126] , [127] , [128] ]. Briefly, the model involved creating a full-thickness segmental defect in the mid-diaphysis of rat femur.…”

“…2 a). The size of the segmental defect size might vary in some studies [ 89 ], and it was subsequently contaminated with a direct injection or a resorbable 10 × 10 × 5 mm 3 segment of type I bovine collagen sponge soaked with a bacteria suspension containing 10 2 [ 88 ] to 1.2 × 10 6 ± 1.9 × 10 5 CFU [ 87 ] of S. aureus . The contamination process lasted for 2, 4 or 9 weeks.…”

“…X-ray and micro-CT images were taken, along with microbial quantification, histological and biomechanical testing, to assess the inflammation stage. The bacteria utilized included ATCC 49525 [ 88 , 121 , 122 ] and its modified bioluminescent strain lux Xen 36 [ 88 , 119 , 123 , 126 ], MSSA isolated from a patient [ 120 ], ATCC 25923 [ 127 ], UAMS-1(ATCC 49230) [ [87] , [88] , [89] , 128 ], coagulase-negative Staphylococci [ 125 ], etc. .…”

Suspension Electrospinning of Decellularized Extracellular Matrix

“…Additionally, fiber microarchitecture can be controlled to vary anisotropy, pore size, and surface texture. 10,[33][34][35][36][37][38] For instance, the fibers can be aligned to support regeneration of anisotropic tissues like skeletal muscle or randomly oriented to support regeneration of isotropic tissue like adipose tissue. The interconnected porosity and high surface area of electrospun scaffolds also provide a tunable platform for cell interaction and infiltration.…”

Osteomyelitis and immune cell phenotypes: a study based on a Mendelian randomisation approach

“…In this study, by analysing data from a large-scale genome-wide association study (GWAS), we assessed potential causal associations between speci c immune cell pro les and osteomyelitis risk (11). The application of this approach not only enhances our understanding of the etiology of osteomyelitis, but also provides a scienti c basis for the development of new therapeutic strategies (12).…”