{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T20:33:56Z","timestamp":1788640436551,"version":"build-2803163510"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001702","name":"AO Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018693","name":"Horizon 2020","doi-asserted-by":"publisher","award":["788753"],"award-info":[{"award-number":["788753"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Acta Biomaterialia"],"published-print":{"date-parts":[[2022,9]]},"DOI":"10.1016\/j.actbio.2022.07.012","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T02:33:29Z","timestamp":1657593209000},"page":"189-197","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Interleukin-1 receptor antagonist enhances the therapeutic efficacy of a low dose of rhBMP-2 in a weight-bearing rat femoral defect model"],"prefix":"10.1016","volume":"149","author":[{"given":"William A.","family":"Lackington","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7148-9569","authenticated-orcid":false,"given":"Dominic","family":"Gehweiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ensi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-887X","authenticated-orcid":false,"given":"Ivan","family":"Zderic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4871-5473","authenticated-orcid":false,"given":"Dirk","family":"Nehrbass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-4202","authenticated-orcid":false,"given":"Stephan","family":"Zeiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0648-5590","authenticated-orcid":false,"given":"Arlyng","family":"Gonz\u00e1lez-V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2030-8005","authenticated-orcid":false,"given":"Fergal J.","family":"O'Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9538-1517","authenticated-orcid":false,"given":"Martin J.","family":"Stoddart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9167-5147","authenticated-orcid":false,"given":"Keith","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.actbio.2022.07.012_bib0001","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S0140-6736(10)62349-5","article-title":"Osteoporosis: now and the future","volume":"377","author":"Rachner","year":"2011","journal-title":"Lancet"},{"key":"10.1016\/j.actbio.2022.07.012_bib0002","series-title":"Racing Surf. Antimicrob. Interface Tissue Eng","first-page":"225","article-title":"Fracture Healing and Progress Towards Successful Repair","author":"Lackington","year":"2020"},{"key":"10.1016\/j.actbio.2022.07.012_bib0003","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/jor.1100180218","article-title":"Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model","volume":"18","author":"Sciadini","year":"2000","journal-title":"J. Orthop. Res. Off. Publ. Orthop. Res. Soc."},{"key":"10.1016\/j.actbio.2022.07.012_bib0004","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2106\/00004623-199274050-00005","article-title":"The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats","volume":"74","author":"Yasko","year":"1992","journal-title":"J. Bone Joint Surg. Am."},{"key":"10.1016\/j.actbio.2022.07.012_bib0005","first-page":"376","volume":"25","author":"Boden","year":"1976"},{"key":"10.1016\/j.actbio.2022.07.012_bib0006","series-title":"Bone Morphogenetic Protein: The State of the Evidence of On-Label and Off-Label Use","author":"Ratko","year":"2010"},{"key":"10.1016\/j.actbio.2022.07.012_bib0007","first-page":"542","volume":"31","author":"Shields","year":"1976"},{"key":"10.1016\/j.actbio.2022.07.012_bib0008","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.addr.2015.04.007","article-title":"Extracellular matrix-inspired growth factor delivery systems for bone regeneration","volume":"94","author":"Martino","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.actbio.2022.07.012_bib0009","series-title":"Incorporation of Hydroxyapatite Into Collagen Scaffolds Enhances the Therapeutic Efficacy of rhBMP-2 in a Weight-Bearing Femoral Defect Model","author":"Lackington","year":"2021"},{"key":"10.1016\/j.actbio.2022.07.012_bib0010","doi-asserted-by":"crossref","first-page":"eaba7602","DOI":"10.1126\/sciadv.aba7602","article-title":"Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling","volume":"6","author":"Julier","year":"2020","journal-title":"Sci. Adv."},{"key":"10.1016\/j.actbio.2022.07.012_bib0011","doi-asserted-by":"crossref","first-page":"11051","DOI":"10.1038\/ncomms11051","article-title":"Inhibition of IL-1R1\/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration","volume":"7","author":"Martino","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.actbio.2022.07.012_bib0012","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/ten.teb.2015.0357","article-title":"A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2","volume":"22","author":"James","year":"2016","journal-title":"Tissue Eng. Part B. Rev."},{"key":"10.1016\/j.actbio.2022.07.012_bib0013","doi-asserted-by":"crossref","first-page":"E933","DOI":"10.1097\/BRS.0000000000002044","article-title":"Dose-dependent Nerve Inflammatory Response to rhBMP-2 in a Rodent Spinal Nerve Model","volume":"42","author":"Liau","year":"2017","journal-title":"Spine (Phila. Pa. 1976)"},{"key":"10.1016\/j.actbio.2022.07.012_bib0014","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40634-017-0079-3","article-title":"The haematoma and its role in bone healing","volume":"4","author":"Schell","year":"2017","journal-title":"J. Exp. Orthop."},{"key":"10.1016\/j.actbio.2022.07.012_bib0015","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"},{"key":"10.1016\/j.actbio.2022.07.012_bib0016","doi-asserted-by":"crossref","first-page":"5482","DOI":"10.7150\/thno.28315","article-title":"Development of an Accurate and Proactive Immunomodulatory Strategy to Improve Bone Substitute Material-Mediated Osteogenesis and Angiogenesis","volume":"8","author":"Zheng","year":"2018","journal-title":"Theranostics"},{"key":"10.1016\/j.actbio.2022.07.012_bib0017","doi-asserted-by":"crossref","first-page":"7562","DOI":"10.1021\/acsabm.0c00801","article-title":"Hydroxyapatite Particle Shape and Size Influence MSC Osteogenesis by Directing the Macrophage Phenotype in Collagen-Hydroxyapatite Scaffolds","volume":"3","author":"Sridharan","year":"2020","journal-title":"ACS Appl. Bio Mater"},{"issue":"46","key":"10.1016\/j.actbio.2022.07.012_bib0018","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1016\/S0020-1383(15)30049-8","article-title":"Risk factors for long bone fracture non-union: a stratification approach based on the level of the existing scientific evidence","volume":"8","author":"Santolini","year":"2015","journal-title":"Injury"},{"key":"10.1016\/j.actbio.2022.07.012_bib0019","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2020.582012","article-title":"Non-viral Gene Delivery of Interleukin-1 Receptor Antagonist Using Collagen-Hydroxyapatite Scaffold Protects Rat BM-MSCs From IL-1\u03b2-Mediated Inhibition of Osteogenesis","volume":"8","author":"Lackington","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.actbio.2022.07.012_bib0020","article-title":"Development and characterization of a predictive microCT-based non-union model in Fischer F344 rats","author":"Hildebrand","year":"2020","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"10.1016\/j.actbio.2022.07.012_bib0021","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1089\/ten.tec.2013.0612","article-title":"Establishment of reproducible, critical-sized, femoral segmental bone defects in rats","volume":"20","author":"Sato","year":"2014","journal-title":"Tissue Eng. Part C. Methods."},{"key":"10.1016\/j.actbio.2022.07.012_bib0022","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2021.712494","article-title":"Differences in Fracture Healing Between Female and Male C57BL\/6J Mice","volume":"12","author":"Haffner-Luntzer","year":"2021","journal-title":"Front. Physiol."},{"key":"10.1016\/j.actbio.2022.07.012_bib0023","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/adma.201103828","article-title":"Innovative collagen nano-hydroxyapatite scaffolds offer a highly efficient non-viral gene delivery platform for stem cell-mediated bone formation","volume":"24","author":"Curtin","year":"2012","journal-title":"Adv. Mater."},{"key":"10.1016\/j.actbio.2022.07.012_bib0024","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1007\/s10856-009-3964-1","article-title":"Development and characterisation of a collagen nano-hydroxyapatite composite scaffold for bone tissue engineering","volume":"21","author":"Cunniffe","year":"2010","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"10.1016\/j.actbio.2022.07.012_bib0025","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1002\/jbm.a.32931","article-title":"The synthesis and characterization of nanophase hydroxyapatite using a novel dispersant-aided precipitation method","volume":"95","author":"Cunniffe","year":"2010","journal-title":"J. Biomed. Mater. Res. A."},{"key":"10.1016\/j.actbio.2022.07.012_bib0026","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1089\/ten.tec.2009.0422","article-title":"Novel freeze-drying methods to produce a range of collagen-glycosaminoglycan scaffolds with tailored mean pore sizes","volume":"16","author":"Haugh","year":"2010","journal-title":"Tissue Eng. Part C. Methods."},{"key":"10.1016\/j.actbio.2022.07.012_bib0027","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0142-9612(03)00630-6","article-title":"Influence of freezing rate on pore structure in freeze-dried collagen-GAG scaffolds","volume":"25","author":"O\u2019Brien","year":"2004","journal-title":"Biomaterials"},{"key":"10.1016\/j.actbio.2022.07.012_bib0028","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1302\/2046-3758.54.2000628","article-title":"The radiographic union scale in tibial (RUST) fractures: reliability of the outcome measure at an independent centre","volume":"5","author":"Leow","year":"2016","journal-title":"Bone Joint Res"},{"key":"10.1016\/j.actbio.2022.07.012_bib0029","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1016\/j.biomaterials.2011.03.063","article-title":"Effects of protein dose and delivery system on BMP-mediated bone regeneration","volume":"32","author":"Boerckel","year":"2011","journal-title":"Biomaterials"},{"key":"10.1016\/j.actbio.2022.07.012_bib0030","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1172\/JCI117187","article-title":"Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats","volume":"93","author":"Kimble","year":"1994","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.actbio.2022.07.012_bib0031","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1172\/JCI200523394","article-title":"IL-1 mediates TNF-induced osteoclastogenesis","volume":"115","author":"Wei","year":"2005","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.actbio.2022.07.012_bib0032","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/intimm\/dxq431","article-title":"IL-1 plays an important role in the bone metabolism under physiological conditions","volume":"22","author":"Lee","year":"2010","journal-title":"Int. Immunol."},{"key":"10.1016\/j.actbio.2022.07.012_bib0033","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/j.biomaterials.2013.11.029","article-title":"The effect of dose on rhBMP-2 signaling, delivered via collagen sponge, on osteoclast activation and in vivo bone resorption","volume":"35","author":"Kim","year":"2014","journal-title":"Biomaterials"},{"key":"10.1016\/j.actbio.2022.07.012_bib0034","article-title":"Influence of Interleukin-1 Beta on Platelet-Poor Plasma Clot Formation: a Potential Impact on Early Bone Healing","volume":"11","author":"Wang","year":"2016","journal-title":"PLoS ONE"},{"key":"10.1016\/j.actbio.2022.07.012_bib0035","doi-asserted-by":"crossref","first-page":"35645","DOI":"10.1038\/srep35645","article-title":"Alteration of blood clot structures by interleukin-1 beta in association with bone defects healing","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.actbio.2022.07.012_bib0036","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/term.2013","article-title":"Controlled release of vascular endothelial growth factor from spray-dried alginate microparticles in collagen-hydroxyapatite scaffolds for promoting vascularization and bone repair","volume":"11","author":"Quinlan","year":"2017","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"10.1016\/j.actbio.2022.07.012_bib0037","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1007\/s11999-013-3438-0","article-title":"Novel microhydroxyapatite particles in a collagen scaffold: a bioactive bone void filler?","volume":"472","author":"Lyons","year":"2014","journal-title":"Clin. Orthop. Relat. Res."},{"key":"10.1016\/j.actbio.2022.07.012_bib0038","doi-asserted-by":"crossref","first-page":"177","DOI":"10.22203\/eCM.v021a14","article-title":"Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics","volume":"21","author":"Wulsten","year":"2011","journal-title":"Eur. Cell. Mater."},{"key":"10.1016\/j.actbio.2022.07.012_bib0039","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1089\/ten.tea.2012.0265","article-title":"Mechanical load modulates the stimulatory effect of BMP2 in a rat nonunion model","volume":"19","author":"Schwarz","year":"2013","journal-title":"Tissue Eng. Part A."},{"key":"10.1016\/j.actbio.2022.07.012_bib0040","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/BOT.0b013e3181b01b2f","article-title":"Ability of recombinant human bone morphogenetic protein 2 to enhance bone healing in the presence of tobramycin: evaluation in a rat segmental defect model","volume":"23","author":"Glatt","year":"2009","journal-title":"J. Orthop. Trauma."},{"key":"10.1016\/j.actbio.2022.07.012_bib0041","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.2106\/JBJS.K.01604","article-title":"Improved healing of large segmental defects in the rat femur by reverse dynamization in the presence of bone morphogenetic protein-2","volume":"94","author":"Glatt","year":"2012","journal-title":"J. Bone Joint Surg. Am."},{"key":"10.1016\/j.actbio.2022.07.012_bib0042","doi-asserted-by":"crossref","first-page":"905","DOI":"10.2106\/00004623-199907000-00002","article-title":"The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats","volume":"81","author":"Lieberman","year":"1999","journal-title":"J. Bone Joint Surg. Am."},{"key":"10.1016\/j.actbio.2022.07.012_bib0043","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1002\/jor.22160","article-title":"BMP induced inflammation: a comparison of rhBMP-7 and rhBMP-2","volume":"30","author":"Lee","year":"2012","journal-title":"J. Orthop. Res. Off. Publ. Orthop. Res. Soc."}],"container-title":["Acta Biomaterialia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1742706122004068?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1742706122004068?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:55:25Z","timestamp":1761674125000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1742706122004068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":43,"alternative-id":["S1742706122004068"],"URL":"https:\/\/doi.org\/10.1016\/j.actbio.2022.07.012","relation":{},"ISSN":["1742-7061"],"issn-type":[{"value":"1742-7061","type":"print"}],"subject":[],"published":{"date-parts":[[2022,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Interleukin-1 receptor antagonist enhances the therapeutic efficacy of a low dose of rhBMP-2 in a weight-bearing rat femoral defect model","name":"articletitle","label":"Article Title"},{"value":"Acta Biomaterialia","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.actbio.2022.07.012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}