{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:50:26Z","timestamp":1791319826175,"version":"4.3.1"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013769","name":"Orthopaedic Trauma Association","doi-asserted-by":"publisher","award":["4122"],"award-info":[{"award-number":["4122"]}],"id":[{"id":"10.13039\/100013769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The field of bone regeneration has primarily focused on investigating fracture healing and nonunion in isolated musculoskeletal injuries. Compared to isolated fractures, which frequently heal well, fractures in patients with multiple bodily injuries (polytrauma) may exhibit impaired healing. While some papers have reported the overall cytokine response to polytrauma conditions, significant gaps in our understanding remain in how fractures heal differently in polytrauma patients. We aimed to characterize fracture healing and the temporal local and systemic immune responses to polytrauma in a murine model of polytrauma composed of a femur fracture combined with isolated chest trauma. We collected serum, bone marrow from the uninjured limb, femur fracture tissue, and lung tissue over 3 weeks to study the local and systemic immune responses and cytokine expression after injury. Immune cell distribution was assessed by flow cytometry. Fracture healing was characterized using microcomputed tomography (microCT), histological staining, immunohistochemistry, mechanical testing, and small angle X\u2010ray scattering. We detected more innate immune cells in the polytrauma group, both locally at the fracture site and systemically, compared to other groups. The percentage of B and T cells was dramatically reduced in the polytrauma group 6\u2009h after injury and remained low throughout the study duration. Fracture healing in the polytrauma group was impaired, evidenced by the formation of a poorly mineralized and dysregulated fracture callus. Our data confirm the early, dysregulated inflammatory state in polytrauma that correlates with disorganized and impaired fracture healing.<\/jats:p>","DOI":"10.1002\/jor.26015","type":"journal-article","created":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T14:39:13Z","timestamp":1731854353000},"page":"603-616","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Polytrauma impairs fracture healing accompanied by increased persistence of innate inflammatory stimuli and reduced adaptive response"],"prefix":"10.1002","volume":"43","author":[{"given":"Augustine Mark","family":"Saiz","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery UC Davis Health Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5089-8693","authenticated-orcid":false,"given":"Maryam","family":"Rahmati","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UC Davis Health Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Charles Henry","family":"Gresham","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UC Davis Health Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony Daniel","family":"Baldini","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UC Davis Health Sacramento California USA"},{"name":"California Northstate University College of Medicine Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Burgan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UC Davis Health Sacramento California USA"},{"name":"Stony Brook Renaissance School of Medicine Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UC Davis Health Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9456-3311","authenticated-orcid":false,"given":"Benjamin","family":"Osipov","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UC Davis Health Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0105-6458","authenticated-orcid":false,"given":"Blaine A.","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery UC Davis Health Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaqif El","family":"Khassawna","sequence":"additional","affiliation":[{"name":"Experimental Trauma Surgery Justus\u2010Liebig University Giessen Giessen Germany"},{"name":"Faculty of Health Sciences University of Applied Sciences Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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