{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:49:51Z","timestamp":1789138191575,"version":"build-2803163510"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0237479","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T18:39:32Z","timestamp":1597343972000},"page":"e0237479","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3551-3204","authenticated-orcid":true,"given":"Manuel","family":"Wei\u00dfenberger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela H.","family":"Wei\u00dfenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Wagenbrenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tizian","family":"Heinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Reboredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris M.","family":"Holzapfel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Rudert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Groll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre F.","family":"Steinert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,8,13]]},"reference":[{"issue":"11","key":"pone.0237479.ref001","first-page":"907","article-title":"Current overview of cartilage regeneration procedures","volume":"46","author":"H Schenker","year":"2017","journal-title":"Der Orthopade"},{"issue":"3","key":"pone.0237479.ref002","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/ar2195","article-title":"Major biological obstacles for persistent cell-based regeneration of articular cartilage.","volume":"9","author":"AF Steinert","year":"2007","journal-title":"Arthritis Res Ther"},{"issue":"3","key":"pone.0237479.ref003","first-page":"263","article-title":"Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers.","volume":"20","author":"AJ Friedenstein","year":"1987","journal-title":"Cell and tissue kinetics"},{"issue":"3","key":"pone.0237479.ref004","doi-asserted-by":"crossref","first-page":"e264","DOI":"10.18295\/squmj.2018.18.03.002","article-title":"Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review.","volume":"18","author":"R Berebichez-Fridman","year":"2018","journal-title":"Sultan Qaboos University medical journal"},{"issue":"3","key":"pone.0237479.ref005","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4103\/0971-5916.198724","article-title":"Cartilage tissue engineering: Role of mesenchymal stem cells along with growth factors & scaffolds","volume":"144","author":"MB Gugjoo","year":"2016","journal-title":"The Indian journal of medical research"},{"key":"pone.0237479.ref006","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jot.2018.09.003","article-title":"Natural hydrogels for cartilage regeneration: Modification, preparation and application","volume":"17","author":"L Li","year":"2019","journal-title":"Journal of orthopaedic translation"},{"issue":"7","key":"pone.0237479.ref007","doi-asserted-by":"crossref","first-page":"497","DOI":"10.2174\/1574888X12666171017160323","article-title":"Application of Hydrogels in Cartilage Tissue Engineering.","volume":"13","author":"X Zhang","year":"2018","journal-title":"Current stem cell research & therapy"},{"issue":"10","key":"pone.0237479.ref008","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1002\/jbm.a.34194","article-title":"An in vitro study of collagen hydrogel to induce the chondrogenic differentiation of mesenchymal stem cells","volume":"100","author":"L Zhang","year":"2012","journal-title":"Journal of biomedical materials research Part A"},{"issue":"6","key":"pone.0237479.ref009","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s13770-018-0135-9","article-title":"Collagen Scaffolds in Cartilage Tissue Engineering and Relevant Approaches for Future Development.","volume":"15","author":"V Irawan","year":"2018","journal-title":"Tissue engineering and regenerative medicine"},{"issue":"12","key":"pone.0237479.ref010","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1177\/0363546511423369","article-title":"A prospective multicenter study on the outcome of type I collagen hydrogel-based autologous chondrocyte implantation (CaReS) for the repair of articular cartilage defects in the knee.","volume":"39","author":"U Schneider","year":"2011","journal-title":"The American journal of sports medicine"},{"issue":"2","key":"pone.0237479.ref011","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.joca.2006.08.008","article-title":"Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells","volume":"15","author":"R Kuroda","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"key":"pone.0237479.ref012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2016.04.018","article-title":"Cell-based tissue engineering strategies used in the clinical repair of articular cartilage","volume":"98","author":"BJ Huang","year":"2016","journal-title":"Biomaterials"},{"issue":"3","key":"pone.0237479.ref013","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/jbm.a.31254","article-title":"Chondrogenic differentiation of human mesenchymal stem cells in collagen type I hydrogels","volume":"83","author":"U Noth","year":"2007","journal-title":"Journal of biomedical materials research Part A"},{"issue":"Suppl 1","key":"pone.0237479.ref014","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1016\/j.injury.2008.01.034","article-title":"Concepts in gene therapy for cartilage repair","volume":"39","author":"AF Steinert","year":"2008","journal-title":"Injury"},{"issue":"5","key":"pone.0237479.ref015","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1089\/ten.tea.2007.0252","article-title":"Enhanced in vitro chondrogenesis of primary mesenchymal stem cells by combined gene transfer","volume":"15","author":"AF Steinert","year":"2009","journal-title":"Tissue Eng Part A"},{"issue":"379 Suppl","key":"pone.0237479.ref016","doi-asserted-by":"crossref","first-page":"S214","DOI":"10.1097\/00003086-200010001-00027","article-title":"Using gene therapy to protect and restore cartilage","author":"CH Evans","year":"2000","journal-title":"Clin Orthop Relat Res"},{"issue":"4","key":"pone.0237479.ref017","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/sj.gt.3302201","article-title":"Gene-based approaches for the repair of articular cartilage","volume":"11","author":"SB Trippel","year":"2004","journal-title":"Gene Ther"},{"issue":"6","key":"pone.0237479.ref018","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.biomaterials.2004.03.005","article-title":"A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells","volume":"26","author":"WJ Li","year":"2005","journal-title":"Biomaterials"},{"issue":"5","key":"pone.0237479.ref019","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s10529-009-9930-7","article-title":"Adenoviral transduction of hTGF-beta1 enhances the chondrogenesis of bone marrow derived stromal cells","volume":"31","author":"W Xia","year":"2009","journal-title":"Biotechnology letters"},{"issue":"12","key":"pone.0237479.ref020","doi-asserted-by":"crossref","first-page":"e116061","DOI":"10.1371\/journal.pone.0116061","article-title":"Demineralized bone matrix combined bone marrow mesenchymal stem cells, bone morphogenetic protein-2 and transforming growth factor-beta3 gene promoted pig cartilage defect repair.","volume":"9","author":"X Wang","year":"2014","journal-title":"PloS one."},{"issue":"6","key":"pone.0237479.ref021","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.knee.2012.03.009","article-title":"Reconstruct large osteochondral defects of the knee with hIGF-1 gene enhanced Mosaicplasty","volume":"19","author":"P Leng","year":"2012","journal-title":"The Knee"},{"issue":"16","key":"pone.0237479.ref022","doi-asserted-by":"crossref","first-page":"3910","DOI":"10.1016\/j.biomaterials.2011.02.014","article-title":"The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells","volume":"32","author":"L Cao","year":"2011","journal-title":"Biomaterials"},{"issue":"3","key":"pone.0237479.ref023","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/scrt113","article-title":"SOX9 gene transfer via safe, stable, replication-defective recombinant adeno-associated virus vectors as a novel, powerful tool to enhance the chondrogenic potential of human mesenchymal stem cells","volume":"3","author":"JK Venkatesan","year":"2012","journal-title":"Stem Cell Res Ther"},{"issue":"9","key":"pone.0237479.ref024","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19092635","article-title":"Improved Chondrogenic Differentiation of rAAV SOX9-Modified Human MSCs Seeded in Fibrin-Polyurethane Scaffolds in a Hydrodynamic Environment.","volume":"19","author":"JK Venkatesan","year":"2018","journal-title":"Int J Mol Sci."},{"issue":"1","key":"pone.0237479.ref025","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/mt.2013.165","article-title":"Regenerating cartilages by engineered ASCs: prolonged TGF-beta3\/BMP-6 expression improved articular cartilage formation and restored zonal structure","volume":"22","author":"CH Lu","year":"2014","journal-title":"Molecular therapy: the journal of the American Society of Gene Therapy"},{"issue":"7","key":"pone.0237479.ref026","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1016\/j.biomaterials.2011.11.050","article-title":"SOX trio-co-transduced adipose stem cells in fibrin gel to enhance cartilage repair and delay the progression of osteoarthritis in the rat","volume":"33","author":"JM Lee","year":"2012","journal-title":"Biomaterials"},{"issue":"5","key":"pone.0237479.ref027","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1302\/0301-620X.89B5.18343","article-title":"Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model","volume":"89","author":"LR Goodrich","year":"2007","journal-title":"The Journal of bone and joint surgery British volume"},{"issue":"1","key":"pone.0237479.ref028","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/jgm.819","article-title":"Local stimulation of articular cartilage repair by transplantation of encapsulated chondrocytes overexpressing human fibroblast growth factor 2 (FGF-2) in vivo.","volume":"8","author":"G Kaul","year":"2006","journal-title":"J Gene Med"},{"issue":"12","key":"pone.0237479.ref029","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1007\/s00167-011-1448-6","article-title":"Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo","volume":"19","author":"P Orth","year":"2011","journal-title":"Knee surgerysports traumatology, arthroscopy: official journal of the ESSKA."},{"issue":"1","key":"pone.0237479.ref030","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s12891-020-3137-4","article-title":"Reduced hypertrophy in vitro after chondrogenic differentiation of adult human mesenchymal stem cells following adenoviral SOX9 gene delivery.","volume":"21","author":"M Weissenberger","year":"2020","journal-title":"BMC musculoskeletal disorders."},{"issue":"3","key":"pone.0237479.ref031","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1128\/JVI.71.3.1842-1849.1997","article-title":"Construction of adenovirus vectors through Cre-lox recombination","volume":"71","author":"S Hardy","year":"1997","journal-title":"Journal of virology"},{"key":"pone.0237479.ref032","first-page":"235","article-title":"Gene transfer to articular chondrocytes with recombinant adenovirus","volume":"215","author":"G Palmer","year":"2003","journal-title":"Methods Mol Biol"},{"issue":"5","key":"pone.0237479.ref033","doi-asserted-by":"crossref","first-page":"R148","DOI":"10.1186\/ar2822","article-title":"Hypertrophy is induced during the in vitro chondrogenic differentiation of human mesenchymal stem cells by bone morphogenetic protein-2 and bone morphogenetic protein-4 gene transfer.","volume":"11","author":"AF Steinert","year":"2009","journal-title":"Arthritis research & therapy."},{"issue":"1","key":"pone.0237479.ref034","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1089\/107632702753503126","article-title":"In vitro engineered cartilage constructs produced by press-coating biodegradable polymer with human mesenchymal stem cells","volume":"8","author":"U Noth","year":"2002","journal-title":"Tissue engineering"},{"issue":"3","key":"pone.0237479.ref035","doi-asserted-by":"crossref","first-page":"225","DOI":"10.25122\/jml-2019-0032","article-title":"Tissue Engineering; Current Status & Futuristic Scope.","volume":"12","author":"P Sharma","year":"2019","journal-title":"Journal of medicine and life"},{"issue":"6","key":"pone.0237479.ref036","first-page":"1289","article-title":"Treatment of Articular Cartilage Defects: Focus on Tissue Engineering","volume":"32","author":"B Zylinska","year":"2018","journal-title":"In vivo (Athens, Greece)."},{"issue":"6","key":"pone.0237479.ref037","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1039\/C8BM00317C","article-title":"The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs).","volume":"6","author":"X Jiang","year":"2018","journal-title":"Biomaterials science."},{"issue":"6","key":"pone.0237479.ref038","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1089\/ten.tea.2009.0531","article-title":"Improving chondrogenesis: potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering","volume":"16","author":"L Kupcsik","year":"2010","journal-title":"Tissue Eng Part A"},{"issue":"7","key":"pone.0237479.ref039","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1089\/ten.2006.0322","article-title":"Three-dimensional microenvironments retain chondrocyte phenotypes during proliferation culture","volume":"13","author":"T Takahashi","year":"2007","journal-title":"Tissue engineering"},{"issue":"3\u20134","key":"pone.0237479.ref040","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1089\/ten.2005.11.597","article-title":"Subculture of chondrocytes on a collagen type I-coated substrate with suppressed cellular dedifferentiation","volume":"11","author":"M Kino-Oka","year":"2005","journal-title":"Tissue engineering"},{"issue":"4","key":"pone.0237479.ref041","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1177\/1947603518769714","article-title":"Human Articular Chondrocytes Retain Their Phenotype in Sustained Hypoxia While Normoxia Promotes Their Immunomodulatory Potential.","volume":"10","author":"C Mennan","year":"2019","journal-title":"Cartilage"},{"key":"pone.0237479.ref042","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.3389\/fphar.2019.01534","article-title":"Scaffold-Based Gene Therapeutics for Osteochondral Tissue Engineering.","volume":"10","author":"X Yan","year":"2019","journal-title":"Front Pharmacol"},{"issue":"3","key":"pone.0237479.ref043","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/bab.1001","article-title":"TGF-\u03b21 gene-engineered mesenchymal stem cells induce rat cartilage regeneration using nonviral gene vector","volume":"59","author":"CX He","year":"2012","journal-title":"Biotechnol Appl Biochem"},{"issue":"9","key":"pone.0237479.ref044","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1002\/jcb.25556","article-title":"Biotechnological Chondroitin a Novel Glycosamminoglycan With Remarkable Biological Function on Human Primary Chondrocytes","volume":"117","author":"A Stellavato","year":"2016","journal-title":"Journal of cellular biochemistry"},{"issue":"4","key":"pone.0237479.ref045","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2174\/1574888X14666181205121658","article-title":"Biomaterials and Gene Therapy: A Smart Combination for MSC Musculoskeletal Engineering.","volume":"14","author":"B Mesure","year":"2019","journal-title":"Current stem cell research & therapy"},{"issue":"4","key":"pone.0237479.ref046","doi-asserted-by":"crossref","first-page":"799","DOI":"10.3390\/jfb3040799","article-title":"Strategic design and fabrication of engineered scaffolds for articular cartilage repair","volume":"3","author":"Z Izadifar","year":"2012","journal-title":"Journal of functional biomaterials"},{"issue":"2","key":"pone.0237479.ref047","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1089\/ten.tea.2009.0168","article-title":"Chondrogenesis of human mesenchymal stem cells by local transforming growth factor-beta delivery in a biphasic resorbable carrier","volume":"16","author":"A Dickhut","year":"2010","journal-title":"Tissue Eng Part A"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0237479","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T18:41:05Z","timestamp":1597344065000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0237479"}},"subtitle":[],"editor":[{"given":"Gianpaolo","family":"Papaccio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,8,13]]},"references-count":47,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0237479","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,13]]}}}