{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:59:46Z","timestamp":1790308786226,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spondylodiscitis\/spondylitis is an intractable disease requiring long\u2010term intravenous antibiotics administration. However, drug delivery is greatly restricted because of the avascular nature in the intervertebral disc, which not only delays recovery but increases antimicrobial resistance and osteomyelitis. The purpose of this study is to elucidate the efficacy of gelatin hydrogel microsphere incorporating cefazolin (GM\u2010CEZ) using a rat spondylodiscitis model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      First, GM\u2010CEZ was characterized by in\u00a0vitro degradability, sustainability, and antimicrobial effects. Second, its efficacy in\u00a0vivo was evaluated using a rat spondylodiscitis model of bioluminescent methicillin\u2010susceptible\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      <\/jats:styled-content>\n                      . Antimicrobial effects were monitored using an in\u00a0vivo imaging system and blood tests. Residual bone volume was evaluated using micro\u2010computed tomography. Immunohistology for angiogenesis\u2010related CD31 and smooth muscle actin was also performed. Third, in\u00a0vivo safety was evaluated using a rat intervertebral disc injection model with blood tests for systemic safety and TUNEL staining for local safety.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In vitro, CEZ was gradually released with GM degradation and antimicrobial effects increased proportionally to the degradation. In\u00a0vivo, single topical injection of GM\u2010CEZ (1\u2009mg GM, 250\u2009\u03bcg\/kg CEZ, 100\u2009\u03bcL collagen) significantly reduced the amount of bacteria with fewer white blood cells 7\u2009days after treatment and bone destruction 28\u2009days after treatment, compared to local administration of CEZ (250\u2009\u03bcg\/kg) and systemic administration of CEZ (25\u2009mg\/kg\/day for 28\u2009days) (all,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Immunopositivity was significantly higher in rats with local GM\u2010CEZ administration than those with local CEZ and systemic CEZ administration (all,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), indicating greater tissue reformation. In\u00a0vivo safety experiments demonstrated no significant myelotoxicity, nephrotoxicity, and local cytotoxicity of GM\u2010CEZ.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The local administration of GM\u2010CEZ using a fraction of the systemic CEZ dose achieved enhanced antimicrobial effects without systemic and local toxicity, suggesting its potential as a promising treatment strategy for pyogenic spondylodiscitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70213","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:26:53Z","timestamp":1788258413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Gelatin Hydrogel\u2010Based Drug\u2010Delivery System Promotes Antimicrobial Efficacy in a Pyogenic Spondylodiscitis Rat Model"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7047-5595","authenticated-orcid":false,"given":"Kunihiko","family":"Miyazaki","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5538-5516","authenticated-orcid":false,"given":"Yutaro","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3007-361X","authenticated-orcid":false,"given":"Takashi","family":"Yurube","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Kobe University Graduate School of Medicine  Kobe 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