Antibiotic-loaded biomaterials (ALBs) have emerged as a potentially useful adjunctive antimicrobial measure for the prevention of infection in open fracture care. A biodegradable thermo-responsive poly(Nisopropylacrylamide) grafted hyaluronic acid (HApN) hydrogel loaded with gentamicin has recently been shown to prevent implant-related infection in a rabbit osteosynthesis model. The primary aim of this study was to determine the influence of this HApN hydrogel on bone healing at an early stage (4 weeks). A rabbit humeral osteotomy model with plating osteosynthesis was used to compare fracture healing in rabbits receiving the hydrogel as compared with control animals. The secondary aim was to observe fracture healing in groups treated with and without antibiotic-loaded hydrogel in the presence of bacterial contamination. In all groups, outcome measures were mechanical stability and histological score, with additional quantitative bacteriology in the inoculated groups. Application of the HApN hydrogel in non-inoculated rabbits did not significantly influence humeral stiffness or histological scores for fracture healing in comparison to controls. In the inoculated groups, animals receiving the bacterial inoculum without hydrogel were culture-positive at euthanasia and found to display lower humeral stiffness values and higher histopathological scores for bacterial presence in comparison with equivalents receiving the gentamicin-loaded HApN hydrogel, which were also infection-free. In summary, our data showed that HApN was an effective antibiotic carrier that did not affect fracture healing. This data supported its suitability for application in fracture care. Addition of osteopromotive compounds could provide further support for accelerating fracture healing in addition to successful infection prophylaxis.
Implantable orthopedic devices have had an enormously positive impact on human health; however, despite best practice, patients are prone develop orthopedic device-related infections (ODRI) that have high treatment failure rates. One barrier to the development of improved treatment options is the lack of an animal model that may serve as a robust preclinical assessment of efficacy. We present a clinically relevant large animal model of chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI that persists despite current clinical practice in medical and surgical treatment at rates equivalent to clinical observations. Furthermore, we showed that an injectable, thermo-responsive hyaluronic acid-based hydrogel loaded with gentamicin and vancomycin outperforms current clinical practice treatment in this model, eliminating bacteria from all animals. These results confirm that local antibiotic delivery with an injectable hydrogel can dramatically increase treatment success rates beyond current clinical practice, with efficacy proven in a robust animal model.
Superconductivity at 33 K in Sr 2 VO 3 FeAs is completely suppressed by small amounts of V doping in Sr 2 VO 3 ͑Fe 0.93͑Ϯ0.01͒ V 0.07͑Ϯ0.01͒ ͒As. The crystal structures and exact stoichiometries are determined by combined neutron powder diffraction and x-ray powder diffraction. Sr 2 VO 3 FeAs is shown to be very sensitive to Fe/V mixing, which interferes with or even suppresses superconductivity. This inhomogeneity may be intrinsic and explains scattered reports regarding T c and reduced superconducting phase fractions in Sr 2 VO 3 FeAs. Neutron-diffraction data collected at 4 K indicate incommensurate magnetic ordering of the V sublattice with a propagation vector q Ϸ͑0,0,0.306͒. This suggests strongly correlated vanadium, which does not contribute significantly to the Fermi surface of Sr 2 VO 3 FeAs.
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