{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T03:37:45Z","timestamp":1758080265932,"version":"3.44.0"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007200","name":"Medizinische Fakult\u00c3\u00a4t, Ruhr-Universit\u00c3\u00a4t Bochum","doi-asserted-by":"publisher","award":["IF-011N-22"],"award-info":[{"award-number":["IF-011N-22"]}],"id":[{"id":"10.13039\/501100007200","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Posttraumatic lymphedema is a common complication after open and closed fractures with soft tissue trauma. Even though there is quite certain consensus about the basic mechanisms of lymphedema formation, the pathophysiology on a cellular and molecular base is largely unknown. Furthermore, there is currently no data on the interaction of lymphedema and bone regeneration. Subsequently, the aim of this study was to establish an animal model specific to posttraumatic lymphedema, which can be used to conduct future investigations into the pathophysiology and bone regeneration in lymphedema.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The test animals (rats)In wild-type Fisher 344 rats were divided into three groups: group one had an isolated bone defect, group two had an isolated soft tissue defect, and group three had a combination of bone and soft tissue trauma.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Using volumetric and circumferential measurements, a significant increase in circumference and volume in the sense of lymphedema could be detected, particularly 3\u20134 weeks after trauma in the groups with soft tissue trauma, whereas the creation of a bony defect did not appear to have a significant influence on the swelling. Microscopic images of the lymphatic drainage pathways verified the lymphatic drainage disorder weeks after soft tissue trauma.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Consequently, the established model can be used to investigate the exact pathophysiology of post-traumatic lymphedema. Furthermore, it seems to be suitable as a model for investigating bone regeneration in manifest lymphedema.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0332067","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T17:24:29Z","timestamp":1758043469000},"page":"e0332067","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishing a new rat model to investigate pathophysiology and bone healing in posttraumatic lymphedema"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-725X","authenticated-orcid":true,"given":"Felix","family":"Reinkemeier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Wallner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius","family":"Drysch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja Verena","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3599-9243","authenticated-orcid":true,"given":"Flemming","family":"Puscz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonca","family":"Steubing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Bakri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Theiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Lehnhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjo\u00f6rn","family":"Behr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes Maximilian","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"pone.0332067.ref001","unstructured":"Wilting J, Bartkowski R, Baumeister R et al. S2k Guideline Diagnostics and Therapy of Lymphedema (05\/2017). access: 10\/24\/2024. https:\/\/register.awmf.org\/assets\/guidelines\/058-001l_S2k_Diagnostik_und_Therapie_der_Lymphoedeme_2019-07.pdf"},{"issue":"1","key":"pone.0332067.ref002","first-page":"1","article-title":"The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology","volume":"46","author":"International Society of Lymphology","year":"2013","journal-title":"Lymphology"},{"key":"pone.0332067.ref003","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/01.sap.0000257149.42922.7e","article-title":"Lymphedema","volume":"59","author":"AG Warren","year":"2007","journal-title":"Ann Plast Surg"},{"key":"pone.0332067.ref004","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.jaad.2017.03.022","article-title":"Lymphedema","volume":"77","author":"AA Grada","year":"2017","journal-title":"J Am Acad Dermatol"},{"key":"pone.0332067.ref005","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1097\/PRS.0000000000004694","article-title":"Lymph flow restoration after tissue replantation and transfer","volume":"142","author":"T Yamamoto","year":"2018","journal-title":"Plast Reconstr Surg"},{"key":"pone.0332067.ref006","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1196\/annals.1413.014","article-title":"Estimating the population burden of lymphedema","volume":"1131","author":"SG Rockson","year":"2008","journal-title":"Ann N Y Acad Sci"},{"issue":"11","key":"pone.0332067.ref007","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.3390\/jpm11111077","article-title":"Posttraumatic Lymphedema after Open Fractures of the Lower Extremity-A Retrospective Cohort Analysis","volume":"11","author":"JM Wagner","year":"2021","journal-title":"J Pers Med"},{"issue":"5","key":"pone.0332067.ref008","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s10147-005-0518-5","article-title":"Treatment of lymphedema with lymphaticovenular anastomoses","volume":"10","author":"T Nagase","year":"2005","journal-title":"Int J Clin Oncol"},{"issue":"6","key":"pone.0332067.ref009","first-page":"424","article-title":"Lympho-reconstructive microsurgery for secondary lymphedema: Consensus of the German-Speaking Society for Microsurgery of Peripheral Nerves and Vessels (DAM) on indication, diagnostic and therapy by lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT)","volume":"51","author":"C Hirche","year":"2019","journal-title":"Handchir Mikrochir Plast Chir"},{"issue":"2","key":"pone.0332067.ref010","first-page":"206","article-title":"Primary lymphedema in children and adolescents: a follow-up study and review","volume":"76","author":"DM Smeltzer","year":"1985","journal-title":"Pediatrics"},{"issue":"1","key":"pone.0332067.ref011","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1158\/2159-8290.CD-15-0023","article-title":"Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer","volume":"6","author":"AW Lund","year":"2016","journal-title":"Cancer Discov"},{"key":"pone.0332067.ref012","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3389\/fimmu.2019.00308","article-title":"Inflammation and lymphatic function","volume":"10","author":"S Schwager","year":"2019","journal-title":"Frontiers in Immunology"},{"issue":"5","key":"pone.0332067.ref013","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1055\/s-2005-865768","article-title":"Lymphatic regeneration following hind limb replantation: an experimental study in the dog","volume":"15","author":"EC Smaropoulos","year":"2005","journal-title":"Eur J Pediatr Surg"},{"issue":"5","key":"pone.0332067.ref014","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1097\/SAP.0000000000001537","article-title":"Quantification of Chronic Lymphedema in a Revised Mouse Model","volume":"81","author":"MG J\u00f8rgensen","year":"2018","journal-title":"Ann Plast Surg"},{"key":"pone.0332067.ref015","article-title":"A revised method for inducing secondary lymphedema in the hindlimb of mice","volume":"153","author":"A Wiinholt","year":"2019","journal-title":"J Vis Exp"},{"issue":"6","key":"pone.0332067.ref016","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1177\/1535370216688570","article-title":"Therapeutic effects of hyaluronidase on acquired lymphedema using a newly developed mouse limb model","volume":"242","author":"K Roh","year":"2017","journal-title":"Exp Biol Med (Maywood)"},{"issue":"1","key":"pone.0332067.ref017","doi-asserted-by":"crossref","DOI":"10.1097\/PRS.0000000000002887","article-title":"Establishment of an Acquired Lymphedema Model in the Mouse Hindlimb: Technical Refinement and Molecular Characteristics","volume":"139","author":"D Iwasaki","year":"2017","journal-title":"Plast Reconstr Surg"},{"issue":"1","key":"pone.0332067.ref018","doi-asserted-by":"crossref","first-page":"18264","DOI":"10.1038\/s41598-019-54201-2","article-title":"A Pre-clinical Animal Model of Secondary Head and Neck Lymphedema","volume":"9","author":"G Daneshgaran","year":"2019","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0332067.ref019","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1089\/lrb.2018.0038","article-title":"Outcomes in Vascularized Lymph Node Transplantation in Rabbits: A Reliable Model for Improving the Surgical Approach to Lymphedema","volume":"17","author":"R Fern\u00e1ndez Pe\u00f1uela","year":"2019","journal-title":"Lymphat Res Biol"},{"issue":"9","key":"pone.0332067.ref020","article-title":"Establishment of a Simple, Reproducible, and Long-lasting Hind Limb Animal Model of Lymphedema","volume":"11","author":"Y Morita","year":"2023","journal-title":"Plast Reconstr Surg Glob Open"},{"key":"pone.0332067.ref021","doi-asserted-by":"crossref","first-page":"1214116","DOI":"10.3389\/fcvm.2023.1214116","article-title":"Development of a rat model of lymphedema and the implantation of a collagen-based medical device for therapeutic intervention","volume":"10","author":"D Nguyen","year":"2023","journal-title":"Front Cardiovasc Med"},{"issue":"4","key":"pone.0332067.ref022","doi-asserted-by":"crossref","DOI":"10.1111\/micc.70009","article-title":"Clinical Relevance of Animal Models of Lymphatic Dysfunction and Lymphedema","volume":"32","author":"PS Podder","year":"2025","journal-title":"Microcirculation"},{"issue":"1","key":"pone.0332067.ref023","doi-asserted-by":"crossref","DOI":"10.1002\/micr.31088","article-title":"Surgical lymphedema models in the mice hindlimb-A systematic review and quality assessment","volume":"44","author":"A Bucan","year":"2024","journal-title":"Microsurgery"},{"issue":"17","key":"pone.0332067.ref024","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.3390\/diagnostics13172822","article-title":"An Evaluation of Lymphedema Using Optical Coherence Tomography: A Rat Limb Model Approach","volume":"13","author":"VV Nikolaev","year":"2023","journal-title":"Diagnostics (Basel)"},{"issue":"4","key":"pone.0332067.ref025","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1089\/lrb.2022.0071","article-title":"Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model","volume":"21","author":"Y Hoshino","year":"2023","journal-title":"Lymphat Res Biol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0332067","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T17:24:35Z","timestamp":1758043475000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0332067"}},"subtitle":[],"editor":[{"given":"Ant\u00f3nio","family":"Machado","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,16]]},"references-count":25,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0332067","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,16]]}}}