The Use of a Biodegradable, Load-Bearing Scaffold as a Carrier for Antibiotics in an Infected Open Fracture Model

Division of Orthopaedics, University of Alabama at Birmingham, Birmingham, AL 35233-3409, USA.
Journal of orthopaedic trauma (Impact Factor: 1.8). 09/2010; 24(9):587-91. DOI: 10.1097/BOT.0b013e3181ed1349
Source: PubMed


Open fractures with bone loss are common, disabling injuries. Biodegradable, load-bearing scaffolds able to carry high concentrations of local antibiotics are an emerging technology to address these injuries. This study investigates the use of such scaffolds with gentamicin (along with bone morphogenetic protein) in an infected rat open fracture model to decrease osteomyelitis and promote fracture healing.
A contaminated open fracture was created in 32 Brown Norway rats. A comminuted femoral fracture was created, followed by crushing, and the 5-mm bone defect was inoculated with Staphylococcus aureus (10 colony-forming units/mL) and Escherichia coli (10 colony-forming units/mL). The scaffold was stabilized in the defect with an intramedullary Kirschner wire. Gentamicin was loaded onto the scaffolds at two doses, either 10 mg (n = 12) or 20 mg (n = 10). Controls (n = 10) received no antibiotics. All three groups had 10 microg bone morphogenetic protein loaded on the scaffold. Serial radiographs were obtained. Microbiologic analysis, microcomputed tomography, and histology were performed.
There was a statistically significant difference in the radiographic evidence of osteomyelitis (P = 0.004) and callus formation (P = 0.021) between the treated and control groups. Bone culture analysis results were not significant for S. aureus (P = 0.29) or E. coli (P = 0.25). There was no difference in the mean scaffold volume or density of the three treatment groups.
Our results suggest that gentamicin applied to a biodegradable scaffold is effective at decreasing radiographically defined osteomyelitis in an infected open fracture.

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Available from: Joseph T Cox, Oct 21, 2014
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    • "Various types of carrier materials have been used based on their ability to achieve sustained bactericidal antibiotic concentrations.6–8 PLGA is a promising biodegradable material that has been used for implantable and injectable controlled-release drug-delivery systems.9,10 "
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    ABSTRACT: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics.
    International Journal of Nanomedicine 09/2014; 9:4347-4355. DOI:10.2147/IJN.S66526 · 4.38 Impact Factor
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    • "In this study, we compared the efficacy of testosterone for fracture repair with that of BMP-2 which is FDA approved for treatment of acute, open tibial shaft fractures as described above and found that testosterone is as effective as BMP-2 in promoting fracture healing. We also used scaffolds that have been shown to effectively deliver BMP-2 and antibiotics to fractured bone [6], [66]. Although the scaffolds used to bridge the fractures in this study were not resorbed during the 35-day period of the investigation, their biodegradable nature had been firmly established [67], [68] and had been shown to be resorbed in 6 months in a canine model [69]. "
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    ABSTRACT: Loss of large bone segments due to fracture resulting from trauma or tumor removal is a common clinical problem. The goal of this study was to evaluate the use of scaffolds containing testosterone, bone morphogenetic protein-2 (BMP-2), or a combination of both for treatment of critical-size segmental bone defects in mice. A 2.5-mm wide osteotomy was created on the left femur of wildtype and androgen receptor knockout (ARKO) mice. Testosterone, BMP-2, or both were delivered locally using a scaffold that bridged the fracture. Results of X-ray imaging showed that in both wildtype and ARKO mice, BMP-2 treatment induced callus formation within 14 days after initiation of the treatment. Testosterone treatment also induced callus formation within 14 days in wildtype but not in ARKO mice. Micro-computed tomography and histological examinations revealed that testosterone treatment caused similar degrees of callus formation as BMP-2 treatment in wildtype mice, but had no such effect in ARKO mice, suggesting that the androgen receptor is required for testosterone to initiate fracture healing. These results demonstrate that testosterone is as effective as BMP-2 in promoting the healing of critical-size segmental defects and that combination therapy with testosterone and BMP-2 is superior to single therapy. Results of this study may provide a foundation to develop a cost effective and efficient therapeutic modality for treatment of bone fractures with segmental defects.
    PLoS ONE 08/2013; 8(8):e70234. DOI:10.1371/journal.pone.0070234 · 3.23 Impact Factor
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    • "In a proof-of-concept study, we evaluated the ability of biofilmdispersive PUR scaffolds augmented with D-AAs to prevent biofilm formation and reduce CFUs in a contaminated rat segmental defect model. Several recent studies have evaluated the effects of local delivery of antibiotics on infection using an acute contamination model, in which the bone graft was placed immediately after contamination of the defect with bacteria [68] [69]. However, preclinical models with an established chronic infection [40] [70] represent a more rigorous test for the efficacy of biofilmdispersive grafts, since they ensure that the bacteria are able to adhere to the surface of the wound and form biofilms [71]. "
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    ABSTRACT: a b s t r a c t Infectious complications of open fractures continue to be a significant factor contributing to non-osseous union and extremity amputation. The persistence of bacteria within biofilms despite meticulous debridement and antibiotic therapy is believed to be a major cause of chronic infection. Considering the difficulties in treating biofilm-associated infections, the use of biofilm dispersal agents as a therapeutic strategy for the prevention of biofilm-associated infections has gained considerable interest. In this study, we investigated whether local delivery of D-Amino Acids (D-AAs), a biofilm dispersal agent, pro-tects scaffolds from contamination and reduces microbial burden within contaminated rat segmental defects in vivo. In vitro testing on biofilms of clinical isolates of Staphylococcus aureus demonstrated that D-Met, D-Phe, D-Pro, and D-Trp were highly effective at dispersing and preventing biofilm formation individually, and the effect was enhanced for an equimolar mixture of D-AAs. Incorporation of D-AAs into polyurethane scaffolds as a mixture (1:1:1 D-Met:D-Pro:D-Trp) significantly reduced bacterial contami-nation on the scaffold surface in vitro and within bone when implanted into contaminated femoral segmental defects. Our results underscore the potential of local delivery of D-AAs for reducing bacterial contamination by targeting bacteria within biofilms, which may represent a treatment strategy for improving healing outcomes associated with open fractures. Published by Elsevier Ltd.
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