{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:46:25Z","timestamp":1787755585783,"version":"build-2784847793"},"reference-count":82,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Gram-negative periprosthetic joint infections (GN-PJIs) present unique challenges. Our aim was to establish a clinically representative GN-PJI model that recapitulates biofilm formation in vivo. We also hypothesized that biofilm formation on the implant surface would affect its ability to osseointegrate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Three-dimensionally-printed medical-grade titanium hip implants were used to replace the femoral heads of male Sprague-Dawley rats. GN-PJI was induced using 2 bioluminescent\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      strains: a reference strain (PA14-\n                      <jats:italic toggle=\"yes\">lux<\/jats:italic>\n                      ) and a mutant biofilm-defective strain (\n                      <jats:italic toggle=\"yes\">\u0394flgK-lux<\/jats:italic>\n                      ). Infection was monitored in real time using an in vivo imaging system (IVIS) and magnetic resonance imaging (MRI). Bacterial loads were quantified utilizing the viable colony count. Biofilm formation at the bone-implant interface was visualized using field-emission scanning electron microscopy (FE-SEM). Implant stability, as an outcome, was directly assessed by quantifying osseointegration using microcomputed tomography, and indirectly assessed by identifying gait-pattern changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Bioluminescence detected by the IVIS was focused on the hip region and demonstrated localized infection, with greater ability of PA14-\n                      <jats:italic toggle=\"yes\">lux<\/jats:italic>\n                      to persist in the model compared with the\n                      <jats:italic toggle=\"yes\">\u0394flgK-lux<\/jats:italic>\n                      strain, which is defective in biofilm formation. This was corroborated by MRI, as PA14-\n                      <jats:italic toggle=\"yes\">lux<\/jats:italic>\n                      induced relatively larger implant-related abscesses. Biofilm formation at the bone-implant interface induced by PA14-\n                      <jats:italic toggle=\"yes\">lux<\/jats:italic>\n                      was visualized using FE-SEM versus defective-biofilm formation by\n                      <jats:italic toggle=\"yes\">\u0394flgK-lux<\/jats:italic>\n                      . Quantitatively, the average viable colony count of the sonicated implants, in colony-forming units\/mL, was 3.77 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      for PA14-\n                      <jats:italic toggle=\"yes\">lux<\/jats:italic>\n                      versus 3.65 \u00d7 10\n                      <jats:sup>3<\/jats:sup>\n                      for\n                      <jats:italic toggle=\"yes\">\u0394flgK-lux,<\/jats:italic>\n                      with a 95% confidence interval around the difference of 1.45 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      to 6.08 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      (p = 0.0025). This difference in the ability to persist in the model was reflected significantly on implant osseointegration, with a mean intersection surface of 4.1 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \u00b1 1.99 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      for PA14-\n                      <jats:italic toggle=\"yes\">lux<\/jats:italic>\n                      versus 6.44 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \u00b1 2.53 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      for\n                      <jats:italic toggle=\"yes\">\u0394flgK-lux<\/jats:italic>\n                      and 7.08 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \u00b1 1.55 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      for the noninfected control (p = 0.048).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>To our knowledge, this proposed, novel in vivo biofilm-based model is the most clinically representative for GN-PJI to date, since animals can bear weight on the implant, poor osseointegration was associated with biofilm formation, and localized PJI was assessed by various modalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>This model will allow for more reliable testing of novel biofilm-targeting therapeutics.<\/jats:p>\n                  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University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9613-0322","authenticated-orcid":false,"given":"Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"Materials Characterization Core Facility, Centre for Advanced Materials Research (CAMaR), University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9097-4113","authenticated-orcid":false,"given":"Kerstin","family":"Ure","sequence":"additional","affiliation":[{"name":"Animal Behavior and Physiology Core, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4623-3534","authenticated-orcid":false,"given":"Clayton W.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, 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