{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:18:42Z","timestamp":1785334722599,"version":"3.55.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"name":"National High Technology Research and Development Program of China","award":["2015AA020302"],"award-info":[{"award-number":["2015AA020302"]}]},{"name":"National Key Research and Development Program of China","award":["2016YFB0700804"],"award-info":[{"award-number":["2016YFB0700804"]}]},{"DOI":"10.13039\/501100001809","name":"NSFC","doi-asserted-by":"publisher","award":["81630065"],"award-info":[{"award-number":["81630065"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"NSFC","doi-asserted-by":"publisher","award":["GZ1094"],"award-info":[{"award-number":["GZ1094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"NSFC","doi-asserted-by":"publisher","award":["81472115"],"award-info":[{"award-number":["81472115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"NSFC","doi-asserted-by":"publisher","award":["81672162"],"award-info":[{"award-number":["81672162"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Scientific and Technological Innovation Team of Zhejiang Province","award":["2013TD11"],"award-info":[{"award-number":["2013TD11"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["2016XZZX001-05"],"award-info":[{"award-number":["2016XZZX001-05"]}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomaterials"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1016\/j.biomaterials.2018.01.016","type":"journal-article","created":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T02:27:43Z","timestamp":1515637663000},"page":"56-68","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":71,"special_numbering":"C","title":["Therapeutic effects of gefitinib-encapsulated thermosensitive injectable hydrogel in intervertebral disc degeneration"],"prefix":"10.1016","volume":"160","author":[{"given":"Zongyou","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianbao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varitsara","family":"Bunpetch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiliang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boon Chin","family":"Heng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.biomaterials.2018.01.016_bib1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrrheum.2015.13","article-title":"Stem cell therapy for intervertebral disc regeneration: obstacles and solutions","volume":"11","author":"Sakai","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"issue":"1","key":"10.1016\/j.biomaterials.2018.01.016_bib2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nrrheum.2013.160","article-title":"Role of cytokines in intervertebral disc degeneration: pain and disc content","volume":"10","author":"Risbud","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"issue":"9","key":"10.1016\/j.biomaterials.2018.01.016_bib3","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrrheum.2014.91","article-title":"Intervertebral disc regeneration: do nutrients lead the way?","volume":"10","author":"Huang","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"issue":"9943","key":"10.1016\/j.biomaterials.2018.01.016_bib4","article-title":"Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010 (vol 380, pg 2163, 2012)","volume":"384","author":"Vos","year":"2014","journal-title":"Lancet"},{"issue":"6","key":"10.1016\/j.biomaterials.2018.01.016_bib5","first-page":"480","article-title":"Diversity of intervertebral disc cells: phenotype and function","volume":"221","author":"Pattappa","year":"2012","journal-title":"J.\u00a0Anat."},{"key":"10.1016\/j.biomaterials.2018.01.016_bib6","first-page":"31","article-title":"Anatomy and Biomechanics of the Spinal Column and Cord","volume":"vol. 109","author":"Miele","year":"2012"},{"issue":"8","key":"10.1016\/j.biomaterials.2018.01.016_bib7","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1097\/00007632-199904150-00005","article-title":"New in\u00a0vivo measurements of pressures in the intervertebral disc in daily life","volume":"24","author":"Wilke","year":"1999","journal-title":"Spine"},{"issue":"1","key":"10.1016\/j.biomaterials.2018.01.016_bib8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.biomaterials.2007.09.018","article-title":"Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels","volume":"29","author":"Richardson","year":"2008","journal-title":"Biomaterials"},{"issue":"4","key":"10.1016\/j.biomaterials.2018.01.016_bib9","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/path.1050","article-title":"Current understanding of cellular and molecular events in intervertebral disc degeneration: implications for therapy","volume":"196","author":"Freemont","year":"2002","journal-title":"J.\u00a0Pathol."},{"issue":"6","key":"10.1016\/j.biomaterials.2018.01.016_bib10","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1302\/0301-620X.78B6.0780965","article-title":"'Stress' distributions inside intervertebral discs. The effects of age and degeneration","volume":"78","author":"Adams","year":"1996","journal-title":"J.\u00a0Bone Joint Surg. British Vol."},{"issue":"1","key":"10.1016\/j.biomaterials.2018.01.016_bib11","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/00007632-199201000-00011","article-title":"Internal intervertebral-disk mechanics as revealed by stress profilometry","volume":"17","author":"Mcnally","year":"1992","journal-title":"Spine"},{"issue":"4","key":"10.1016\/j.biomaterials.2018.01.016_bib12","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.jbiomech.2004.07.039","article-title":"Biomechanical comparison between fusion of two vertebrae and implantation of an artificial intervertebral disc","volume":"39","author":"Denoziere","year":"2006","journal-title":"J.\u00a0Biomech."},{"issue":"2","key":"10.1016\/j.biomaterials.2018.01.016_bib13","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s00586-002-0493-8","article-title":"Complications in lumbar fusion surgery for chronic low back pain: comparison of three surgical techniques used in a prospective randomized study. A report from the Swedish Lumbar Spine Study Group","volume":"12","author":"Fritzell","year":"2003","journal-title":"Eur. Spine J."},{"issue":"6 Suppl","key":"10.1016\/j.biomaterials.2018.01.016_bib14","doi-asserted-by":"crossref","first-page":"190S","DOI":"10.1016\/j.spinee.2004.07.007","article-title":"Adjacent segment degeneration and adjacent segment disease: the consequences of spinal fusion?","volume":"4","author":"Hilibrand","year":"2004","journal-title":"Spine J. Offic. J. North Am. Spine Soc."},{"issue":"2","key":"10.1016\/j.biomaterials.2018.01.016_bib15","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1227\/01.NEU.0000337574.58662.E2","article-title":"Recurrent disc herniation and long-term back pain after primary lumbar discectomy: review of outcomes reported for limited versus aggressive disc removal","volume":"64","author":"McGirt","year":"2009","journal-title":"Neurosurgery"},{"issue":"22","key":"10.1016\/j.biomaterials.2018.01.016_bib16","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1097\/BRS.0b013e3182544a8a","article-title":"Homing of mesenchymal stem cells in induced degenerative intervertebral discs in a whole organ culture system","volume":"37","author":"Illien-Junger","year":"2012","journal-title":"Spine"},{"issue":"7","key":"10.1016\/j.biomaterials.2018.01.016_bib17","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/nrm1962","article-title":"EGF-ERBB signalling: towards the systems level","volume":"7","author":"Citri","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"33","key":"10.1016\/j.biomaterials.2018.01.016_bib18","doi-asserted-by":"crossref","first-page":"11740","DOI":"10.1073\/pnas.0505171102","article-title":"Targeted disruption of Mig-6 in the mouse genome leads to early onset degenerative joint disease","volume":"102","author":"Zhang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"3","key":"10.1016\/j.biomaterials.2018.01.016_bib19","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/ar4233","article-title":"Transient anabolic effects accompany epidermal growth factor receptor signal activation in articular cartilage in\u00a0vivo","volume":"15","author":"Shepard","year":"2013","journal-title":"Arthritis Res. Ther."},{"issue":"11","key":"10.1016\/j.biomaterials.2018.01.016_bib20","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1002\/art.22968","article-title":"Transforming growth factor alpha suppression of articular chondrocyte phenotype and Sox9 expression in a rat model of osteoarthritis","volume":"56","author":"Appleton","year":"2007","journal-title":"Arthritis Rheum."},{"issue":"11","key":"10.1016\/j.biomaterials.2018.01.016_bib21","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1002\/jbmr.502","article-title":"The critical role of the epidermal growth factor receptor in endochondral ossification","volume":"26","author":"Zhang","year":"2011","journal-title":"J.\u00a0Bone Miner. Res. Offi. J. Am. Soc. Bone Miner. Res."},{"issue":"6","key":"10.1016\/j.biomaterials.2018.01.016_bib22","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.jhep.2004.08.024","article-title":"Targeting the epidermal growth factor receptor by gefitinib for treatment of hepatocellular carcinoma","volume":"41","author":"Hopfner","year":"2004","journal-title":"J.\u00a0Hepatol."},{"issue":"2","key":"10.1016\/j.biomaterials.2018.01.016_bib23","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/hep.20538","article-title":"Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis","volume":"41","author":"Schiffer","year":"2005","journal-title":"Hepatology"},{"issue":"2","key":"10.1016\/j.biomaterials.2018.01.016_bib24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/term.500","article-title":"Hydrogels in acellular and cellular strategies for intervertebral disc regeneration","volume":"7","author":"Pereira","year":"2013","journal-title":"J\u00a0Tissue Eng Regen M"},{"issue":"18","key":"10.1016\/j.biomaterials.2018.01.016_bib25","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1097\/BRS.0b013e31817c64a9","article-title":"A\u00a0simple disc degeneration model induced by percutaneous needle puncture in the rat tail","volume":"33","author":"Han","year":"2008","journal-title":"Spine"},{"issue":"17","key":"10.1016\/j.biomaterials.2018.01.016_bib26","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1097\/00007632-200109010-00011","article-title":"Magnetic resonance classification of lumbar intervertebral disc degeneration","volume":"26","author":"Pfirrmann","year":"2001","journal-title":"Spine"},{"key":"10.1016\/j.biomaterials.2018.01.016_bib27","doi-asserted-by":"crossref","first-page":"236","DOI":"10.22203\/eCM.v028a16","article-title":"Col2CreER(T2), a mouse model for a chondrocyte-specific and inducible gene deletion","volume":"28","author":"Chen","year":"2014","journal-title":"Eur. Cell. Mater."},{"issue":"24","key":"10.1016\/j.biomaterials.2018.01.016_bib28","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1097\/00007632-199712150-00001","article-title":"1997 Volvo Award winner in basic science studies - immunohistologic markers for age-related changes of human lumbar intervertebral discs","volume":"22","author":"Nerlich","year":"1997","journal-title":"Spine"},{"issue":"36","key":"10.1016\/j.biomaterials.2018.01.016_bib29","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1016\/j.biomaterials.2009.08.058","article-title":"Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering","volume":"30","author":"Tan","year":"2009","journal-title":"Biomaterials"},{"key":"10.1016\/j.biomaterials.2018.01.016_bib30","doi-asserted-by":"crossref","first-page":"5063","DOI":"10.1016\/j.actbio.2012.09.034","article-title":"Injectable and biodegradable thermosensitive hydrogels loaded with PHBHHx nanoparticles for the sustained and controlled release of insulin","volume":"9","author":"Peng","year":"2013","journal-title":"Acta Biomater."},{"key":"10.1016\/j.biomaterials.2018.01.016_bib31","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0736-0266(02)00098-0","article-title":"An in\u00a0vivo model of degenerative disc disease","volume":"21","author":"Norcross","year":"2003","journal-title":"J.\u00a0Orthop. Res."},{"issue":"3","key":"10.1016\/j.biomaterials.2018.01.016_bib32","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00256-008-0611-8","article-title":"Relationship of Modic type 1 change with disc degeneration: a prospective MRI study","volume":"38","author":"Luoma","year":"2009","journal-title":"Skeletal Radiol."},{"issue":"2","key":"10.1016\/j.biomaterials.2018.01.016_bib33","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/1097-4644(20010501)81:2<368::AID-JCB1051>3.0.CO;2-J","article-title":"Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in\u00a0vitro","volume":"81","author":"Jakob","year":"2001","journal-title":"J.\u00a0Cell. Biochem."},{"issue":"11","key":"10.1016\/j.biomaterials.2018.01.016_bib34","doi-asserted-by":"crossref","first-page":"9691","DOI":"10.1074\/jbc.M211360200","article-title":"Differentiation status-dependent regulation of cyclooxygenase-2 expression and prostaglandin E2 production by epidermal growth factor via mitogen-activated protein kinase in articular chondrocytes","volume":"278","author":"Huh","year":"2003","journal-title":"J.\u00a0Biol. Chem."},{"issue":"4","key":"10.1016\/j.biomaterials.2018.01.016_bib35","first-page":"593","article-title":"Activation of epidermal growth factor receptor gene is involved in transforming growth factor-beta-mediated fibronectin expression in a chondrocyte progenitor cell line","volume":"25","author":"Takeda","year":"2010","journal-title":"Int. J. Mol. Med."},{"issue":"6","key":"10.1016\/j.biomaterials.2018.01.016_bib36","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1002\/art.22711","article-title":"Global analyses of gene expression in early experimental osteoarthritis","volume":"56","author":"Appleton","year":"2007","journal-title":"Arthritis Rheum."},{"issue":"1","key":"10.1016\/j.biomaterials.2018.01.016_bib37","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/labinvest.2009.111","article-title":"Rho\/ROCK and MEK\/ERK activation by transforming growth factor-alpha induces articular cartilage degradation","volume":"90","author":"Appleton","year":"2010","journal-title":"Lab. Invest."},{"key":"10.1016\/j.biomaterials.2018.01.016_bib38","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0736-0266(02)00098-0","article-title":"An in\u00a0vivo model of degenerative disc disease","volume":"21","author":"Norcross","year":"2003","journal-title":"J.\u00a0Orthop. Res."},{"issue":"1","key":"10.1016\/j.biomaterials.2018.01.016_bib39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the pathogenesis of disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell"},{"issue":"6","key":"10.1016\/j.biomaterials.2018.01.016_bib40","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.cell.2013.08.015","article-title":"EGFR-Mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and Tumor Chemoresistance","volume":"154","author":"Wei","year":"2013","journal-title":"Cell"},{"issue":"6","key":"10.1016\/j.biomaterials.2018.01.016_bib41","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1002\/jcb.24465","article-title":"mTOR inhibitors radiosensitize PTEN-deficient non-small-cell lung cancer cells harboring an EGFR activating mutation by inducing autophagy","volume":"114","author":"Kim","year":"2013","journal-title":"J.\u00a0Cell. Biochem."},{"issue":"12","key":"10.1016\/j.biomaterials.2018.01.016_bib42","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/j.joca.2013.10.002","article-title":"Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression","volume":"21","author":"Ma","year":"2013","journal-title":"Osteoarthritis Cartilage"},{"issue":"3","key":"10.1016\/j.biomaterials.2018.01.016_bib43","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3892\/ijmm.2015.2280","article-title":"Autophagy attenuates the catabolic effect during inflammatory conditions in nucleus pulposus cells, as sustained by NF-kappa B and JNK inhibition","volume":"36","author":"Xu","year":"2015","journal-title":"Int. J. Mol. Med."},{"issue":"3","key":"10.1016\/j.biomaterials.2018.01.016_bib44","first-page":"111","article-title":"Analgesic effect of gefitinib in the treatment of non-small cell lung cancer","volume":"4","author":"Moryl","year":"2006","journal-title":"J.\u00a0Support Oncol."}],"container-title":["Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S014296121830022X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S014296121830022X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T16:31:15Z","timestamp":1758904275000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S014296121830022X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":44,"alternative-id":["S014296121830022X"],"URL":"https:\/\/doi.org\/10.1016\/j.biomaterials.2018.01.016","relation":{},"ISSN":["0142-9612"],"issn-type":[{"value":"0142-9612","type":"print"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Therapeutic effects of gefitinib-encapsulated thermosensitive injectable hydrogel in intervertebral disc degeneration","name":"articletitle","label":"Article Title"},{"value":"Biomaterials","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biomaterials.2018.01.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}