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            <subfield code="a">10.1016/j.jcpa.2016.11.073</subfield>
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            <subfield code="2">sideral</subfield>
            <subfield code="a">98333</subfield>
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            <subfield code="a">ART-2017-98333</subfield>
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            <subfield code="a">eng</subfield>
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        <datafield tag="100" ind1=" " ind2=" ">
            <subfield code="a">Gimeno, M.</subfield>
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        <datafield tag="245" ind1=" " ind2=" ">
            <subfield code="a">Biocompatibility Studies of Local Antibiotic-eluting Devices for Orthopaedic Applications</subfield>
        </datafield>
        <datafield tag="260" ind1=" " ind2=" ">
            <subfield code="c">2017</subfield>
        </datafield>
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            <subfield code="a">Access copy available to the general public</subfield>
            <subfield code="f">Unrestricted</subfield>
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            <subfield code="a">Introduction: Efficient local antibiotic-eluting devices could be an alternative for delivery of locally therapeutic antibiotics into tissues, avoiding bacterial contamination on implanted materials and minimizing side effects. A proper assessment of biocompatibility of the biomaterials used is important to improve safety after implantation. We present cytotoxicological and implantation tests results to evaluate biocompatibility of two drug-eluting systems with potential use in orthopaedic implants.

Materials and Methods: Cytotoxicological studies were carried out by evaluating the in-vitro dose-dependent effect of cefazolin and linezolid on fibroblasts, keratinocytes, macrophages and osteoblasts. Cells were incubated with antibiotic concentrations ranging from 0.25 to 1.5 mg/ml. Cellular viability was assessed by the Alamar blue test. Cell cycle and apoptosis were measured by flow cytometry. Short-term implantation tests were performed in an ovine model to assess the local effects of the device. Two implants were used: (1) a macroporous stainless steel reservoir loaded with linezolid and (2) stainless steel pins with orifices drilled in the reservoir wall loaded with cefazolin. Implants were placed in sheep tibias. Tissues were studied by pathological means, determining the local effect and tissue response from the implant. (Ethical committee approval number: PI36/14)

Results: Cytotoxic effects of cefazolin and linezolid were only found at 1.5 mg/ml on keratinocytes and osteoblasts, respectively. There were no significant changes on cell cycle and apoptosis at 1.0 mg/ml. Sheep with both antibiotic-loaded implants did not show local or systemic adverse effects.

Conclusions: These results showed no potential toxic effects for the designed devices. However, the antibiotic local concentration should not exceed 1.0 mg/ml.</subfield>
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            <subfield code="9">info:eu-repo/semantics/openAccess</subfield>
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            <subfield code="u">http://creativecommons.org/licenses/by-nc-nd/3.0/es/</subfield>
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            <subfield code="b">2017</subfield>
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            <subfield code="a">VETERINARY SCIENCES</subfield>
            <subfield code="b">46 / 140 = 0.329</subfield>
            <subfield code="c">2017</subfield>
            <subfield code="d">Q2</subfield>
            <subfield code="e">T1</subfield>
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        <datafield tag="591" ind1=" " ind2=" ">
            <subfield code="a">PATHOLOGY</subfield>
            <subfield code="b">58 / 79 = 0.734</subfield>
            <subfield code="c">2017</subfield>
            <subfield code="d">Q3</subfield>
            <subfield code="e">T3</subfield>
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        <datafield tag="592" ind1=" " ind2=" ">
            <subfield code="a">0.594</subfield>
            <subfield code="b">2017</subfield>
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        <datafield tag="593" ind1=" " ind2=" ">
            <subfield code="a">Veterinary (miscellaneous)</subfield>
            <subfield code="c">2017</subfield>
            <subfield code="d">Q2</subfield>
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        <datafield tag="593" ind1=" " ind2=" ">
            <subfield code="a">Pathology and Forensic Medicine</subfield>
            <subfield code="c">2017</subfield>
            <subfield code="d">Q2</subfield>
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        <datafield tag="700" ind1=" " ind2=" ">
            <subfield code="0">(orcid)0000-0002-9210-6026</subfield>
            <subfield code="a">Pinczowski, P.</subfield>
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        <datafield tag="700" ind1=" " ind2=" ">
            <subfield code="0">(orcid)0000-0003-2293-363X</subfield>
            <subfield code="a">Mendoza, G.</subfield>
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        <datafield tag="700" ind1=" " ind2=" ">
            <subfield code="0">(orcid)0000-0002-8712-2275</subfield>
            <subfield code="a">Vázquez, F.J.</subfield>
            <subfield code="u">Universidad de Zaragoza</subfield>
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        <datafield tag="700" ind1=" " ind2=" ">
            <subfield code="0">(orcid)0000-0002-8133-2124</subfield>
            <subfield code="a">Pérez, M.</subfield>
            <subfield code="u">Universidad de Zaragoza</subfield>
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        <datafield tag="700" ind1=" " ind2=" ">
            <subfield code="0">(orcid)0000-0002-6178-4801</subfield>
            <subfield code="a">Asín, J.</subfield>
            <subfield code="u">Universidad de Zaragoza</subfield>
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        <datafield tag="700" ind1=" " ind2=" ">
            <subfield code="0">(orcid)0000-0002-8701-9745</subfield>
            <subfield code="a">Santamaría, J.</subfield>
            <subfield code="u">Universidad de Zaragoza</subfield>
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        <datafield tag="700" ind1=" " ind2=" ">
            <subfield code="0">(orcid)0000-0003-3165-0156</subfield>
            <subfield code="a">Arruebo, M.</subfield>
            <subfield code="u">Universidad de Zaragoza</subfield>
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        <datafield tag="700" ind1=" " ind2=" ">
            <subfield code="0">(orcid)0000-0002-2053-9842</subfield>
            <subfield code="a">Luján, L.</subfield>
            <subfield code="u">Universidad de Zaragoza</subfield>
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            <subfield code="1">1001</subfield>
            <subfield code="2">025</subfield>
            <subfield code="a">Universidad de Zaragoza</subfield>
            <subfield code="b">Dpto. Anatom.,Embri.Genét.Ani.</subfield>
            <subfield code="c">Área Anatom.Anatom.Patológ.Com</subfield>
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            <subfield code="1">1009</subfield>
            <subfield code="2">773</subfield>
            <subfield code="a">Universidad de Zaragoza</subfield>
            <subfield code="b">Dpto. Patología Animal</subfield>
            <subfield code="c">Área Sanidad Animal</subfield>
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        <datafield tag="710" ind1="2" ind2=" ">
            <subfield code="1">5005</subfield>
            <subfield code="2">555</subfield>
            <subfield code="a">Universidad de Zaragoza</subfield>
            <subfield code="b">Dpto. Ing.Quím.Tecnol.Med.Amb.</subfield>
            <subfield code="c">Área Ingeniería Química</subfield>
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            <subfield code="a">Universidad de Zaragoza</subfield>
            <subfield code="b">Dpto. Patología Animal</subfield>
            <subfield code="c">Área Medicina y Cirugía Animal</subfield>
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        <datafield tag="773" ind1=" " ind2=" ">
            <subfield code="g">156, 1 (2017), 77</subfield>
            <subfield code="p">J. Comp. Pathol.</subfield>
            <subfield code="t">JOURNAL OF COMPARATIVE PATHOLOGY</subfield>
            <subfield code="x">0021-9975</subfield>
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