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: 1.54). 09/2010; 24(9):587-91. DOI: 10.1097/BOT.0b013e3181ed1349
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Joseph T Cox, Oct 21, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite advances in traumatic wound care and management, infections remain a leading cause of mortality,morbidity and economic disruption in millions of wound patients around the world. Animal models have become standard tools for studying a wide array of external traumatic wound infections and testing new antimicrobial strategies. Animal models of external traumatic wound infections reported by different investigators vary in animal species used, microorganism strains, the number of microorganisms applied, the size of the wounds and for burn infections, the length of time the heated object or liquid is in contact with the skin.Methods: This review covers experimental infections in animal models of surgical wounds, skin abrasions, burns, lacerations,excisional wounds and open fractures. As antibiotic resistance continues to increase,more new antimicrobial approaches are urgently needed.These should be tested using standard protocols for infections in external traumatic wounds in animal models.
    Virulence 07/2011; 2(4):296-315. DOI:10.4161/viru.2.4.16840 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Infection is a common complication of open fractures. Systemic antibiotics often cause adverse events before eradication of infected bone occurs. The local delivery of antibiotics and the use of implants that deliver both growth factors and antimicrobials are ways to circumvent systemic toxicity while decreasing infection and to reach extremely high levels required to treat bacterial biofilms. When choosing an antibiotic for a local delivery system, one should consider the effect that the antibiotic has on cell viability and osteogenic activity. To address this concern, osteoblasts were treated with 21 different antibiotics over 8 concentrations from 0 to 5000 µg/ml. Osteoblast deoxyribonucleic acid content and alkaline phosphatase activity (ALP) were measured to determine cell number and osteogenic activity, respectively. Antibiotics that caused the greatest decrement include rifampin, minocycline, doxycycline, nafcillin, penicillin, ciprofloxacin, colistin methanesulfonate, and gentamicin; their cell number and ALP were significantly less than control at drug concentrations ≤ 200 µg/ml. Conversely, amikacin, tobramycin, and vancomycin were the least cytotoxic and did not appreciably affect cell number and ALP until very high concentrations were used. This comprehensive evaluation of numerous antibiotics' effects on osteoblast viability and activity will enable clinicians and researchers to choose the optimal antibiotic for treatment of infection and maintenance of healthy host bone.
    Journal of Orthopaedic Research 07/2011; 29(7):1070-4. DOI:10.1002/jor.21343 · 2.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Segmental bone loss remains a challenging clinical problem. A frequent mitigating factor is inadequate blood supply. Small molecules that activate the hypoxia-inducible factor pathway can be used to stimulate angiogenesis. We investigated an approach to promote healing using angiogenic and osteogenic compounds in combination with a biodegradable, weightbearing scaffold. Adult rats underwent removal of a 5-mm segment of femur stabilized by a cylindrical biodegradable implant and intramedullary fixation. Treatment groups included 1) saline (negative control); 2) desferrioxamine (DFO, a hypoxia-inducible factor activator; 3) low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) (5 μg); 4) DFO and low-dose rhBMP-2 (5 μg); or 5) rh-BMP-2 (10 μg). Angiography was used to evaluate vascularity. Bone healing was assessed by radiographs, microcomputed tomography, histology, and biomechanical testing. Increased vascularity was seen at 6 weeks in the DFO treatment group. There appeared to be increased bone bridging as assessed by radiographic scores and microcomputed tomography in the BMP groups, although the quantification of bone volume did not show statistically significant differences. Biomechanical testing revealed improved stiffness in the treatment groups. DFO improved angiogenesis and stiffness of bone healing in segmental defects. BMP improved radiographic scores and stiffness. Use of angiogenic compounds in segmental bone loss is promising. Activation of the hypoxia-inducible factor pathway may prove useful for bone defects, particularly where impaired blood supply exists.The low-cost approach could be useful in segmental bone defects clinically.
    Journal of orthopaedic trauma 08/2011; 25(8):472-6. DOI:10.1097/BOT.0b013e31822588d8 · 1.54 Impact Factor
Show more