{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:05:14Z","timestamp":1779919514944,"version":"3.53.1"},"reference-count":54,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine & Pharmacotherapy"],"published-print":{"date-parts":[[2023,12]]},"DOI":"10.1016\/j.biopha.2023.115697","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:44:13Z","timestamp":1697676253000},"page":"115697","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Cilostazol promotes blood vessel formation and bone regeneration in a murine non-union model"],"prefix":"10.1016","volume":"168","author":[{"given":"Maximilian M.","family":"Menger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Bleimehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Scheuer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Hans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-3710","authenticated-orcid":false,"given":"Dominik","family":"Saul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Ehnert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Menger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Histing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias W.","family":"Laschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrrheum.2014.164","article-title":"Fracture healing: mechanisms and interventions","volume":"11","author":"Einhorn","year":"2015","journal-title":"Nat. Rev. Rheuma"},{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2106\/JBJS.J.00795","article-title":"Temporal and spatial vascularization patterns of unions and nonunions: role of vascular endothelial growth factor and bone morphogenetic proteins","volume":"94","author":"Garcia","year":"2012","journal-title":"J. Bone Jt. Surg. Am."},{"key":"10.1016\/j.biopha.2023.115697_bib3","article-title":"Vascularization strategies in the prevention of non-union formation","author":"Menger","year":"2020","journal-title":"Tissue Eng. Part B Rev."},{"key":"10.1016\/j.biopha.2023.115697_bib4","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/00003086-198904000-00017","article-title":"Ilizarov treatment of tibial nonunions with bone loss","volume":"241","author":"Paley","year":"1989","journal-title":"Clin. Orthop. Relat. Res"},{"key":"10.1016\/j.biopha.2023.115697_bib5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1097\/00003086-198111000-00005","article-title":"The treatment of nonunions without electrical stimulation","volume":"161","author":"Weber","year":"1981","journal-title":"Clin. Orthop. Relat. Res"},{"issue":"7","key":"10.1016\/j.biopha.2023.115697_bib6","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1359\/JBMR.050301","article-title":"Angiogenesis is required for successful bone induction during distraction osteogenesis","volume":"20","author":"Fang","year":"2005","journal-title":"J. Bone Min. Res"},{"issue":"Suppl 3","key":"10.1016\/j.biopha.2023.115697_bib7","first-page":"140","article-title":"Nonsteroidal anti-inflammatory drug-induced fracture nonunion: an inhibition of angiogenesis?","volume":"88","author":"Murnaghan","year":"2006","journal-title":"J. Bone Jt. Surg. Am."},{"key":"10.1016\/j.biopha.2023.115697_bib8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22203\/eCM.v022a01","article-title":"Local inhibition of angiogenesis results in an atrophic non-union in a rat osteotomy model","volume":"22","author":"Fassbender","year":"2011","journal-title":"Eur. Cell Mater."},{"issue":"7A","key":"10.1016\/j.biopha.2023.115697_bib9","first-page":"1201","article-title":"Hemodynamic effects of the antithrombotic drug cilostazol in chronic arterial occlusion in the extremities","volume":"35","author":"Kamiya","year":"1985","journal-title":"Arzneimittelforschung"},{"issue":"3","key":"10.1016\/j.biopha.2023.115697_bib10","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1097\/00005344-200009000-00011","article-title":"Inhibition of adenosine uptake and augmentation of ischemia-induced increase of interstitial adenosine by cilostazol, an agent to treat intermittent claudication","volume":"36","author":"Liu","year":"2000","journal-title":"J. Cardiovasc Pharm."},{"issue":"2","key":"10.1016\/j.biopha.2023.115697_bib11","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1124\/jpet.111.181180","article-title":"Combinatorial effect of probucol and cilostazol in focal ischemic mice with hypercholesterolemia","volume":"338","author":"Kim","year":"2011","journal-title":"J. Pharm. Exp. Ther."},{"key":"10.1016\/j.biopha.2023.115697_bib12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-4419-1241-1_12","article-title":"The effects of cilostazol on tissue oxygenation upon an ischemic-reperfusion injury in the mouse cerebrum","volume":"662","author":"Morikawa","year":"2010","journal-title":"Adv. Exp. Med Biol."},{"issue":"6","key":"10.1016\/j.biopha.2023.115697_bib13","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1067\/mva.2002.129654","article-title":"Pharmacologic therapy for peripheral arterial disease and claudication","volume":"36","author":"Hiatt","year":"2002","journal-title":"J. Vasc. Surg."},{"issue":"3","key":"10.1016\/j.biopha.2023.115697_bib14","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.ijcard.2012.03.103","article-title":"Cilostazol promotes angiogenesis after peripheral ischemia through a VEGF-dependent mechanism","volume":"167","author":"Biscetti","year":"2013","journal-title":"Int J. Cardiol."},{"key":"10.1016\/j.biopha.2023.115697_bib15","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3390\/ijms232314839","article-title":"Effects of cilostazol on angiogenesis in diabetes through adiponectin\/adiponectin receptors\/sirtuin1 signaling pathway","volume":"23","author":"Tseng","year":"2022","journal-title":"Int J. Mol. Sci."},{"issue":"3","key":"10.1016\/j.biopha.2023.115697_bib16","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1177\/1074248419897852","article-title":"Cilostazol mediates immune responses and affects angiogenesis during the acute phase of hind limb ischemia in a mouse model","volume":"25","author":"Paronis","year":"2020","journal-title":"J. Cardiovasc Pharm. Ther."},{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/jor.20658","article-title":"Effect of cell-based VEGF gene therapy on healing of a segmental bone defect","volume":"27","author":"Li","year":"2009","journal-title":"J. Orthop. Res"},{"issue":"11","key":"10.1016\/j.biopha.2023.115697_bib18","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1359\/JBMR.050708","article-title":"VEGF improves, whereas sFlt1 inhibits, BMP2-induced bone formation and bone healing through modulation of angiogenesis","volume":"20","author":"Peng","year":"2005","journal-title":"J. Bone Min. Res"},{"issue":"3","key":"10.1016\/j.biopha.2023.115697_bib19","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/S8756-3282(02)00839-6","article-title":"A phosphodiesterase inhibitor, pentoxifylline, enhances the bone morphogenetic protein-4 (BMP-4)-dependent differentiation of osteoprogenitor cells","volume":"31","author":"Tsutsumimoto","year":"2002","journal-title":"Bone"},{"issue":"2","key":"10.1016\/j.biopha.2023.115697_bib20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1359\/jbmr.2002.17.2.249","article-title":"Involvement of phosphodiesterase isozymes in osteoblastic differentiation","volume":"17","author":"Wakabayashi","year":"2002","journal-title":"J. Bone Min. Res"},{"issue":"12","key":"10.1016\/j.biopha.2023.115697_bib21","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1002\/jor.22967","article-title":"Stimulation of angiogenesis by cilostazol accelerates fracture healing in mice","volume":"33","author":"Herath","year":"2015","journal-title":"J. Orthop. Res"},{"issue":"5","key":"10.1016\/j.biopha.2023.115697_bib22","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1093\/gerona\/glab304","article-title":"Establishment of a reliable model to study the failure of fracture healing in aged mice","volume":"77","author":"Menger","year":"2022","journal-title":"J. Gerontol. A Biol. Sci. Med Sci."},{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib23","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jss.2007.09.013","article-title":"Development of a reliable non-union model in mice","volume":"147","author":"Garcia","year":"2008","journal-title":"J. Surg. Res"},{"issue":"9","key":"10.1016\/j.biopha.2023.115697_bib24","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1002\/jor.20849","article-title":"Ex vivo analysis of rotational stiffness of different osteosynthesis techniques in mouse femur fracture","volume":"27","author":"Histing","year":"2009","journal-title":"J. Orthop. Res"},{"issue":"10","key":"10.1016\/j.biopha.2023.115697_bib25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0239517","article-title":"Short-term molecular and cellular effects of ischemia\/reperfusion on vascularized lymph node flaps in rats","volume":"15","author":"Frueh","year":"2020","journal-title":"PLoS One"},{"issue":"3","key":"10.1016\/j.biopha.2023.115697_bib26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.7150\/thno.10155","article-title":"Prediction of tumor recurrence and therapy monitoring using ultrasound-guided photoacoustic imaging","volume":"5","author":"Mallidi","year":"2015","journal-title":"Theranostics"},{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib27","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1148\/radiol.14140654","article-title":"Photoacoustic imaging of vascular hemodynamics: validation with blood oxygenation level-dependent MR imaging","volume":"275","author":"Rich","year":"2015","journal-title":"Radiology"},{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib28","doi-asserted-by":"crossref","first-page":"10977","DOI":"10.1038\/s41598-018-29252-6","article-title":"Prevascularization of dermal substitutes with adipose tissue-derived microvascular fragments enhances early skin grafting","volume":"8","author":"Frueh","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.biopha.2023.115697_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.pacs.2022.100409","article-title":"Photoacoustic imaging for the study of oxygen saturation and total hemoglobin in bone healing and non-union formation","volume":"28","author":"Menger","year":"2022","journal-title":"Photoacoustics"},{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib30","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3109\/17453674.2013.773123","article-title":"Augmentation of autologous bone graft by a combination of bone morphogenic protein and bisphosphonate increased both callus volume and strength","volume":"84","author":"Bosemark","year":"2013","journal-title":"Acta Orthop."},{"issue":"2","key":"10.1016\/j.biopha.2023.115697_bib31","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.bone.2008.10.039","article-title":"Micro-computed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function","volume":"44","author":"Morgan","year":"2009","journal-title":"Bone"},{"issue":"10","key":"10.1016\/j.biopha.2023.115697_bib32","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1359\/JBMR.050702","article-title":"Application of histomorphometric methods to the study of bone repair","volume":"20","author":"Gerstenfeld","year":"2005","journal-title":"J. Bone Min. Res"},{"issue":"3","key":"10.1016\/j.biopha.2023.115697_bib33","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s10456-022-09832-x","article-title":"The vascularization paradox of non-union formation","volume":"25","author":"Menger","year":"2022","journal-title":"Angiogenesis"},{"issue":"2","key":"10.1016\/j.biopha.2023.115697_bib34","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4103\/0019-5413.50844","article-title":"Bone stimulation for fracture healing: What's all the fuss?","volume":"43","author":"Victoria","year":"2009","journal-title":"Indian J. Orthop."},{"key":"10.1016\/j.biopha.2023.115697_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2022.116475","article-title":"Comparison of two non-union models with damaged periosteum in mice: Segmental defect and pin-clip fixation versus transverse fracture and K-wire stabilization","volume":"162","author":"Menger","year":"2022","journal-title":"Bone"},{"key":"10.1016\/j.biopha.2023.115697_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22203\/eCM.v026a01","article-title":"Rodent animal models of delayed bone healing and non-union formation: a comprehensive review","volume":"26","author":"Garcia","year":"2013","journal-title":"Eur. Cell Mater."},{"key":"10.1016\/j.biopha.2023.115697_bib37","doi-asserted-by":"crossref","first-page":"100","DOI":"10.22203\/eCM.v015a08","article-title":"Osteogenesis and angiogenesis: the potential for engineering bone","volume":"15","author":"Kanczler","year":"2008","journal-title":"Eur. Cell Mater."},{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib38","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/jor.24170","article-title":"Cellular biology of fracture healing","volume":"37","author":"Bahney","year":"2019","journal-title":"J. Orthop. Res"},{"issue":"6","key":"10.1016\/j.biopha.2023.115697_bib39","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/S8756-3282(01)00608-1","article-title":"Prevention of fracture healing in rats by an inhibitor of angiogenesis","volume":"29","author":"Hausman","year":"2001","journal-title":"Bone"},{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib40","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11420-009-9129-4","article-title":"Vascular endothelial growth factor: an essential component of angiogenesis and fracture healing","volume":"6","author":"Beamer","year":"2010","journal-title":"HSS J."},{"issue":"Suppl 2","key":"10.1016\/j.biopha.2023.115697_bib41","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1016\/S0020-1383(08)70015-9","article-title":"Fracture vascularity and bone healing: a systematic review of the role of VEGF","volume":"39","author":"Keramaris","year":"2008","journal-title":"Injury"},{"key":"10.1016\/j.biopha.2023.115697_bib42","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/978-1-4419-0298-6_7","article-title":"RANKL\/RANK as key factors for osteoclast development and bone loss in arthropathies","volume":"649","author":"Leibbrandt","year":"2009","journal-title":"Adv. Exp. Med Biol."},{"issue":"2","key":"10.1016\/j.biopha.2023.115697_bib43","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","article-title":"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"issue":"2","key":"10.1016\/j.biopha.2023.115697_bib44","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0092-8674(00)80209-3","article-title":"Osteoprotegerin: a novel secreted protein involved in the regulation of bone density","volume":"89","author":"Simonet","year":"1997","journal-title":"Cell"},{"issue":"2","key":"10.1016\/j.biopha.2023.115697_bib45","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1359\/jbmr.081113","article-title":"Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing","volume":"24","author":"Gerstenfeld","year":"2009","journal-title":"J. Bone Min. Res"},{"issue":"6","key":"10.1016\/j.biopha.2023.115697_bib46","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00223-012-9601-x","article-title":"Pantoprazole, a proton pump inhibitor, delays fracture healing in mice","volume":"90","author":"Histing","year":"2012","journal-title":"Calcif. Tissue Int"},{"issue":"1","key":"10.1016\/j.biopha.2023.115697_bib47","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jss.2010.08.036","article-title":"Melatonin impairs fracture healing by suppressing RANKL-mediated bone remodeling","volume":"173","author":"Histing","year":"2012","journal-title":"J. Surg. Res"},{"issue":"8","key":"10.1016\/j.biopha.2023.115697_bib48","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.molmed.2014.06.001","article-title":"Osteoclasts: more than 'bone eaters'","volume":"20","author":"Charles","year":"2014","journal-title":"Trends Mol. Med"},{"issue":"23","key":"10.1016\/j.biopha.2023.115697_bib49","first-page":"5421","article-title":"Vascular endothelial growth factor up-regulates its receptor fms-like tyrosine kinase 1 (FLT-1) and a soluble variant of FLT-1 in human vascular endothelial cells","volume":"57","author":"Barleon","year":"1997","journal-title":"Cancer Res"},{"issue":"8","key":"10.1016\/j.biopha.2023.115697_bib50","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1242\/dev.129.8.1893","article-title":"Skeletal defects in VEGF(120\/120) mice reveal multiple roles for VEGF in skeletogenesis","volume":"129","author":"Zelzer","year":"2002","journal-title":"Development"},{"issue":"7","key":"10.1016\/j.biopha.2023.115697_bib51","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.matbio.2008.06.005","article-title":"VEGF enhancement of osteoclast survival and bone resorption involves VEGF receptor-2 signaling and beta3-integrin","volume":"27","author":"Yang","year":"2008","journal-title":"Matrix Biol."},{"key":"10.1016\/j.biopha.2023.115697_bib52","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bone.2016.02.020","article-title":"Inflammation, fracture and bone repair","volume":"86","author":"Loi","year":"2016","journal-title":"Bone"},{"key":"10.1016\/j.biopha.2023.115697_bib53","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.3389\/fimmu.2019.02443","article-title":"Compromised bone healing in aged rats is associated with impaired M2 macrophage function","volume":"10","author":"Loffler","year":"2019","journal-title":"Front Immunol."},{"key":"10.1016\/j.biopha.2023.115697_bib54","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bone.2015.10.019","article-title":"Macrophages in bone fracture healing: Their essential role in endochondral ossification","volume":"106","author":"Schlundt","year":"2018","journal-title":"Bone"}],"container-title":["Biomedicine & Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332223014956?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332223014956?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:23:27Z","timestamp":1779917007000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0753332223014956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":54,"alternative-id":["S0753332223014956"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2023.115697","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Cilostazol promotes blood vessel formation and bone regeneration in a murine non-union model","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2023.115697","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"115697"}}