Article

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: 1.78). 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.

0 Bookmarks
 · 
130 Views
  • [Show abstract] [Hide abstract]
    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 · 4.20 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Source
    [Show abstract] [Hide abstract]
    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.
    Biomaterials 01/2013; · 8.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Research on incorporation of both growth factors and silver (Ag) into hydroxyapatite (HA) coatings on metallic implant surfaces for enhancing osteoinductivity and antibacterial properties is a challenging work. Generally, Ag nanoparticles are easy to agglomerate and lead to a large increase in local Ag concentration, which could potentially affect cell activity. On the other hand, growth factors immobilization requires mild processing conditions so as to maintain their activities. In this study, bone morphology protein-2 (BMP-2) and Ag nanoparticle contained HA coatings were prepared on Ti surfaces by combining electrochemical deposition (ED) of Ag and electrostatic immobilization of BMP-2. During the ED process, chitosan (CS) was selected as the stabilizing agent to chelate Ag ions and generate Ag nanoparticles that are uniformly distributed in the coatings. CS also reduces Ag toxicity while retaining its antibacterial activity. Afterwards, a BMP/heparin solution was absorbed on the CS/Ag/HA coatings. Consequently, BMP-2 was immobilized on the coatings by the electrostatic attraction between CS, heparin, and BMP-2. Sustained release of BMP-2 and Ag ions from HA coatings was successfully demonstrated for a long period. Results of antibacterial tests indicate that the CS/Ag/HA coatings have high antibacterial properties against both S. epidermidis and E. coli. Osteoblasts (OB) culture reveals that the CS/Ag/HA coatings exhibit good biocompatibility. Bone marrow stromal cells (BMSCs) culture indicates that the BMP/CS/Ag/HA coatings have good osteoinductivity and promote the differentiation of BMSCs. Ti bars with BMP/CS/Ag/HA coatings were implanted into the femur of rabbits to evaluate the osteoinductivity of the coatings. Results indicate that BMP/CS/Ag/HA coatings favor bone formation in vivo. In summary, this study presents a convenient and effective method for the incorporation of growth factors and antibacterial agents into HA coatings. This method can be utilized to modify a variety of metallic implant surfaces.
    ACS Applied Materials & Interfaces 04/2014; 6(11). DOI:10.1021/am501428e · 5.90 Impact Factor

Full-text (2 Sources)

Download
19 Downloads
Available from
Oct 21, 2014