{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:33:45Z","timestamp":1792730025355,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&D Plan","award":["2018YFC1105900"],"award-info":[{"award-number":["2018YFC1105900"]}]},{"name":"Sichuan Province Major Scientific & Technological Achievements Transformation Demonstration Project","award":["2016CZYD0004"],"award-info":[{"award-number":["2016CZYD0004"]}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science & Technology","doi-asserted-by":"publisher","award":["2017SZ0001"],"award-info":[{"award-number":["2017SZ0001"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Province Key R&D Program","award":["2019YFS0007"],"award-info":[{"award-number":["2019YFS0007"]}]},{"name":"Young Elite Scientists Sponsorship Program","award":["2017QNRC001"],"award-info":[{"award-number":["2017QNRC001"]}]},{"name":"Sichuan University Innovation Spark Project","award":["2018SCUH0089"],"award-info":[{"award-number":["2018SCUH0089"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The self-healing capacity of cartilage was limited due to absence of vascular, nervous and lymphatic systems. Although many clinical treatments have been used in cartilage defect repair and shown a promising repair result in short term, however, regeneration of complete zonal structure with physiological function, reconstruction cartilage homeostasis and maintaining long-term repair was still an unbridgeable chasm. Cartilage has complex zonal structure and multiple physiological functions, especially, superficial and calcified cartilage played an important role in keeping homeostasis. To address this hurdle of regenerating superficial and calcified cartilage, injectable tissue-induced type I collagen (Col I) hydrogel-encapsulated BMSCs was chosen to repair cartilage damage. After 1 month implantation, the results demonstrated that Col I gel was able to induce BMSCs differentiation into chondrocytes, and formed hyaline-like cartilage and the superficial layer with lubrication function. After 3 months post-surgery, chondrocytes at the bottom of the cartilage layer would undergo hypertrophy and promote the regeneration of calcified cartilage. Six months later, a continuous anatomical tidemark and complete calcified interface were restored. The regeneration of neo-hyaline cartilage was similar with adjacent normal tissue on the thickness of the cartilage, matrix secretion, collagen type and arrangement. Complete multilayer zonal structure with physiological function remodeling indicated that BMSCs-assisted injectable Col I hydrogel could reconstruct cartilage homeostasis and maintain long-term therapeutic effect.<\/jats:p>","DOI":"10.1093\/rb\/rbz028","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T14:10:47Z","timestamp":1574431847000},"page":"35-45","source":"Crossref","is-referenced-by-count":45,"title":["BMSCs-assisted injectable Col I hydrogel-regenerated cartilage defect by reconstructing superficial and calcified cartilage"],"prefix":"10.1093","volume":"7","author":[{"given":"Hanxu","family":"Cai","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilei","family":"Wang","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Yao","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Development and Related Disease of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, 20 Renmin South Road, Chengdu 610041, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Development and Related Disease of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, 20 Renmin South Road, Chengdu 610041, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-2616","authenticated-orcid":false,"given":"Yong","family":"Sun","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liang","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiang","family":"Fan","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingdong","family":"Zhang","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,22]]},"reference":[{"key":"2020030307594759400_rbz028-B1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrrheum.2014.157","article-title":"Repair and tissue engineering techniques for articular cartilage","volume":"11","author":"Makris","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"2020030307594759400_rbz028-B2","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1126\/science.1222454","article-title":"Unlike bone, cartilage regeneration remains elusive","volume":"338","author":"Huey","year":"2012","journal-title":"Science"},{"key":"2020030307594759400_rbz028-B3","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nrrheum.2013.29","article-title":"Functional articular cartilage repair: here, near, or is the best approach not yet clear","volume":"9","author":"Mastbergen","year":"2013","journal-title":"Nat Rev Rheumatol"},{"key":"2020030307594759400_rbz028-B4","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.biotechadv.2012.11.004","article-title":"Osteochondral tissue engineering: current strategies and challenges","volume":"31","author":"Nukavarapu","year":"2013","journal-title":"Biotechnol Adv"},{"key":"2020030307594759400_rbz028-B5","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.ijpharm.2016.10.035","article-title":"Tailoring biomaterial scaffolds for osteochondral repair","volume":"523","author":"Camarero-Espinosa","year":"2017","journal-title":"Int J Pharm"},{"key":"2020030307594759400_rbz028-B6","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrrheum.2011.109","article-title":"Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA","volume":"7","author":"Lotz","year":"2011","journal-title":"Nat Rev Rheumatol"},{"key":"2020030307594759400_rbz028-B7","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.bone.2012.03.023","article-title":"Effects of aging on articular cartilage homeostasis","volume":"51","author":"Lotz","year":"2012","journal-title":"Bone"},{"key":"2020030307594759400_rbz028-B8","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1002\/art.24036","article-title":"Zonal gene expression of chondrocytes in osteoarthritic cartilage","volume":"58","author":"Fukui","year":"2008","journal-title":"Arthritis Rheum"},{"key":"2020030307594759400_rbz028-B9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/jbmr.508","article-title":"Proteoglycan 4: a dynamic regulator of skeletogenesis and parathyroid hormone skeletal anabolism","volume":"27","author":"Novince","year":"2012","journal-title":"J Bone Miner Res"},{"key":"2020030307594759400_rbz028-B10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/jor.22207","article-title":"Impact of proteoglycan-4 and parathyroid hormone on articular cartilage","volume":"31","author":"Novince","year":"2013","journal-title":"J Orthop Res"},{"key":"2020030307594759400_rbz028-B11","doi-asserted-by":"crossref","first-page":"5852","DOI":"10.1073\/pnas.1219289110","article-title":"Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis","volume":"110","author":"Waller","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020030307594759400_rbz028-B12","first-page":"1","article-title":"Proteoglycan 4 expression protects against the development of osteoarthritis","volume":"176","author":"Ruan","year":"2013","journal-title":"Transl Med Sci"},{"key":"2020030307594759400_rbz028-B13","doi-asserted-by":"crossref","first-page":"20296","DOI":"10.1021\/acsami.8b03445","article-title":"Multilayered scaffold with a compact interfacial layer enhances osteochondral defect repair","volume":"10","author":"Jia","year":"2018","journal-title":"ACS Appl Mater Interfaces"},{"key":"2020030307594759400_rbz028-B14","doi-asserted-by":"crossref","first-page":"085","DOI":"10.1055\/s-0032-1319782","article-title":"The cartilage-bone interface","volume":"25","author":"Hoemann","year":"2012","journal-title":"J Knee Surg"},{"key":"2020030307594759400_rbz028-B15","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1002\/stem.534","article-title":"Stem cells and cartilage development: complexities of a simple tissue","volume":"28","author":"Hollander","year":"2010","journal-title":"Stem Cells"},{"key":"2020030307594759400_rbz028-B16","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1002\/jbm.a.35309","article-title":"Redifferentiation of dedifferentiated chondrocytes in a novel three-dimensional microcavitary hydrogel","volume":"103","author":"Zeng","year":"2015","journal-title":"J Biomed Mater Res"},{"key":"2020030307594759400_rbz028-B17","doi-asserted-by":"crossref","first-page":"6871","DOI":"10.1016\/j.biomaterials.2014.04.107","article-title":"Effects of spreading areas and aspect ratios of single cells on dedifferentiation of chondrocytes","volume":"35","author":"Cao","year":"2014","journal-title":"Biomaterials"},{"key":"2020030307594759400_rbz028-B18","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.joca.2006.07.006","article-title":"Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair","volume":"15","author":"Holland","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"key":"2020030307594759400_rbz028-B19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.injury.2008.01.036","article-title":"Smart biomaterials for tissue engineering of cartilage","volume":"39","author":"Stoop","year":"2008","journal-title":"Injury"},{"key":"2020030307594759400_rbz028-B20","doi-asserted-by":"crossref","first-page":"S171","DOI":"10.1097\/00003086-200110001-00017","article-title":"Chondrogenesis in cartilage repair is induced by members of the transforming growth factor-beta super family","volume":"391","author":"Hunziker","year":"2001","journal-title":"Clin Orthop Relat Res"},{"key":"2020030307594759400_rbz028-B21","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1002\/aic.690491202","article-title":"Advances in biomaterials, drug delivery, and bionanotechnology","volume":"49","author":"Langer","year":"2003","journal-title":"AIChE J"},{"key":"2020030307594759400_rbz028-B22","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1007\/s00264-015-2695-9","article-title":"Short-term follow up after implantation of a cell-free collagen type I matrix for the treatment of large cartilage defects of the knee","volume":"39","author":"Roessler","year":"2015","journal-title":"Int Orthop"},{"key":"2020030307594759400_rbz028-B23","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.biomaterials.2012.10.027","article-title":"The use of type 1 collagen scaffold containing stromal cell-derived factor-1 to create a matrix environment conducive to partial-thickness cartilage defects repair","volume":"34","author":"Zhang","year":"2013","journal-title":"Biomaterials"},{"key":"2020030307594759400_rbz028-B24","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1002\/jbm.a.35356","article-title":"Current strategies in multiphasic scaffold design for osteochondral tissue engineering: a review","volume":"103","author":"Yousefi","year":"2015","journal-title":"J Biomed Mater Res"},{"key":"2020030307594759400_rbz028-B25","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":"Noth","year":"2007","journal-title":"J Biomed Mater Res"},{"key":"2020030307594759400_rbz028-B26","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1515\/bmt-2013-0076","article-title":"Chondrogenic predifferentiation of human mesenchymal stem cells in collagen type I hydrogels","volume":"59","author":"Fensky","year":"2014","journal-title":"Biomed Tech"},{"key":"2020030307594759400_rbz028-B27","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/jbm.a.32588","article-title":"Chondrogenic differentiation of mesenchymal stem cells induced by collagen-based hydrogel: an in vivo study","volume":"93","author":"Zheng","year":"2010","journal-title":"J Biomed Mater Res A"},{"key":"2020030307594759400_rbz028-B28","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":"Zhang","year":"2012","journal-title":"J Biomed Mater Res"},{"key":"2020030307594759400_rbz028-B29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/acs.biomac.6b01619","article-title":"Injectable and 3D bioprinted polysaccharide hydrogels: from cartilage to osteochondral tissue engineering","volume":"18","author":"Radhakrishnan","year":"2017","journal-title":"Biomacromolecules"},{"key":"2020030307594759400_rbz028-B30","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.biomaterials.2018.11.017","article-title":"An injectable continuous stratified structurally and functionally biomimetic construct for enhancing osteochondral regeneration","volume":"192","author":"Zhu","year":"2019","journal-title":"Biomaterials"},{"key":"2020030307594759400_rbz028-B31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/boneres.2017.14","article-title":"Injectable hydrogels for cartilage and bone tissue engineering","volume":"5","author":"Liu","year":"2017","journal-title":"Bone Res"},{"key":"2020030307594759400_rbz028-B32","year":"2010"},{"key":"2020030307594759400_rbz028-B33","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.joca.2007.05.005","article-title":"International Cartilage Repair Society (ICRS) and Oswestry macroscopic cartilage evaluation scores validated for use in Autologous Chondrocyte Implantation (ACI) and microfracture","volume":"15","author":"Van den Borne","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"key":"2020030307594759400_rbz028-B34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.actbio.2009.07.041","article-title":"Repair of osteochondral defects with biodegradable hydrogel composites encapsulating marrow mesenchymal stem cells in a rabbit model","volume":"6","author":"Guo","year":"2010","journal-title":"Acta Biomater"},{"key":"2020030307594759400_rbz028-B35","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s10735-005-3283-x","article-title":"The tidemark of the chondro-osseous junction of the normal human knee joint","volume":"36","author":"Lyons","year":"2005","journal-title":"J Mol Hist"},{"key":"2020030307594759400_rbz028-B36","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.joca.2012.09.009","article-title":"Dual inversion recovery ultra short echo time (DIR-UTE) imaging and quantification of the zone of calcified cartilage (ZCC)","volume":"21","author":"Du","year":"2013","journal-title":"Osteoarthritis Cartilage"},{"key":"2020030307594759400_rbz028-B37","first-page":"379","article-title":"Cellular, molecular, and matrix changes in cartilage during aging and osteoarthritis","volume":"6","author":"Horton","year":"2006","journal-title":"J Musculoskelet Neuronal Interact"}],"container-title":["Regenerative Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/rb\/article-pdf\/7\/1\/35\/32757773\/rbz028.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/rb\/article-pdf\/7\/1\/35\/32757773\/rbz028.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T15:38:48Z","timestamp":1722094728000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/rb\/article\/7\/1\/35\/5637846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,22]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,11,22]]},"published-print":{"date-parts":[[2020,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/rb\/rbz028","relation":{},"ISSN":["2056-3418","2056-3426"],"issn-type":[{"value":"2056-3418","type":"print"},{"value":"2056-3426","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,2]]},"published":{"date-parts":[[2019,11,22]]}}}