{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:32:41Z","timestamp":1788496361515,"version":"build-2803163510"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["12\/RC\/2278"],"award-info":[{"award-number":["12\/RC\/2278"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["17\/SP\/4721"],"award-info":[{"award-number":["17\/SP\/4721"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Articular cartilage (AC) possesses a limited healing potential, meaning that untreated focal joint defects typically progress, leading to the development of degenerative diseases such as osteoarthritis. Several clinical strategies exist that aim to regenerate AC; however, recapitulation of a fully functional, load-bearing tissue remains a significant challenge. This can be attributed, at least in part, to a paucity of biomaterials that truly mimic the native tissue and provide appropriate cues to direct its regeneration. The main structural component of articular cartilage, type II collagen, does not readily gelate at body temperature, challenging the development of cartilage extracellular matrix (cECM)-derived injectable hydrogels and bioinks for AC tissue engineering and bioprinting applications. Here, we describe the development and rheological characterisation of a methacrylated cartilage ECM-based hydrogel\/bioink (cECM-MA), which could be photocrosslinked when exposed to ultraviolet (UV) light. Functionalisation of the collagen backbone with methacryloyl groups had a negligible effect on triple helix stability, as demonstrated by circular dichroism spectroscopy. These cECM-MA bioinks demonstrated shear-thinning properties and could be loaded with bone marrow mesenchymal stem cells (BM-MSCs), micro-extruded to generate self-supporting 3D constructs of predefined size and shape, and then photocrosslinked using UV light. Analysis of the cell-laden constructs showed that the BM-MSCs were viable post-printing and underwent chondrogenesis in vitro, generating a tissue rich in sulphated glycosaminoglycans and collagens. These results support the use of methacrylated, tissue-specific ECM-derived hydrogels as bioinks for 3D bioprinting and\/or as injectables for cartilage tissue engineering applications.<\/jats:p>","DOI":"10.3390\/biom12020216","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T21:59:55Z","timestamp":1643320795000},"page":"216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue Engineering"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3637-6619","authenticated-orcid":false,"given":"Kevin","family":"Behan","sequence":"first","affiliation":[{"name":"Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland"},{"name":"Department of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-6579","authenticated-orcid":false,"given":"Alexandre","family":"Dufour","sequence":"additional","affiliation":[{"name":"Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland"},{"name":"Department of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orquidea","family":"Garcia","sequence":"additional","affiliation":[{"name":"Johnson & Johnson Services, Inc., 31 Technology Drive, Irvine, CA 92618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kelly","sequence":"additional","affiliation":[{"name":"Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland"},{"name":"Department of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin, D02 PN40 Dublin, Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre (AMBER), CRANN, Naughton Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland"},{"name":"Department of Anatomy, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1016\/j.biomaterials.2006.03.050","article-title":"Cartilage tissue engineering with silk scaffolds and human articular chondrocytes","volume":"27","author":"Wang","year":"2006","journal-title":"Biomaterials"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/s41584-019-0255-1","article-title":"Surgical and tissue engineering strategies for articular cartilage and meniscus repair","volume":"15","author":"Kwon","year":"2019","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fsurg.2018.00070","article-title":"Cartilage tissue engineering using stem cells and bioprinting technology\u2014Barriers to clinical translation","volume":"5","author":"Francis","year":"2018","journal-title":"Front. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.biomaterials.2015.02.026","article-title":"Injectable glycopolypeptide hydrogels as biomimetic scaffolds for cartilage tissue engineering","volume":"51","author":"Ren","year":"2015","journal-title":"Biomaterials"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3650","DOI":"10.1016\/j.actbio.2014.04.031","article-title":"Self-crosslinked oxidized alginate\/gelatin hydrogel as injectable, adhesive biomimetic scaffolds for cartilage regeneration","volume":"10","author":"Balakrishnan","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/jbm.a.32869","article-title":"Genipin-cross-linked collagen\/chitosan biomimetic scaffolds for articular cartilage tissue engineering applications","volume":"95","author":"Yan","year":"2010","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1700298","DOI":"10.1002\/adhm.201700298","article-title":"3D bioprinting for cartilage and osteochondral tissue engineering","volume":"6","author":"Daly","year":"2017","journal-title":"Adv. Healthc. Mater."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/s41467-021-21029-2","article-title":"3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels","volume":"12","author":"Daly","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Badylak, S.F. (2002). The extracellular matrix as a scaffold for tissue reconstruction. Seminars in Cell & Developmental Biology, Elsevier.","DOI":"10.1016\/S1084952102000940"},{"key":"ref_10","first-page":"3675","article-title":"Decellularization of tissues and organs","volume":"27","author":"Gilbert","year":"2006","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1016\/j.biomaterials.2011.01.057","article-title":"An overview of tissue and whole organ decellularization processes","volume":"32","author":"Crapo","year":"2011","journal-title":"Biomaterials"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9295","DOI":"10.1016\/j.biomaterials.2013.08.054","article-title":"Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix","volume":"34","author":"Yang","year":"2013","journal-title":"Biomaterials"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.actbio.2016.11.046","article-title":"Anatomical region-dependent enhancement of 3-dimensional chondrogenic differentiation of human mesenchymal stem cells by soluble meniscus extracellular matrix","volume":"49","author":"Rothrauff","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_14","first-page":"e1826","article-title":"Meniscus ECM-functionalised hydrogels containing infrapatellar fat pad-derived stem cells for bioprinting of regionally defined meniscal tissue","volume":"12","author":"Romanazzo","year":"2017","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s13770-017-0104-8","article-title":"Development of printable natural cartilage matrix bioink for 3D printing of irregular tissue shape","volume":"15","author":"Jung","year":"2017","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.actbio.2020.11.029","article-title":"A photo-crosslinkable cartilage-derived extracellular matrix bioink for auricular cartilage tissue engineering","volume":"121","author":"Visscher","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_17","unstructured":"Doherty, S. (2021, December 10). The Development of Region-Specific Decellularized Meniscus Bioinks for 3D Bioprinting Applications. Available online: https:\/\/ir.lib.uwo.ca\/etd\/7606."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1039\/C8BM01246F","article-title":"Advances in crosslinking strategies of biomedical hydrogels","volume":"7","author":"Hu","year":"2019","journal-title":"Biomater. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2002931","DOI":"10.1002\/smll.202002931","article-title":"Crosslinking strategies for 3D bioprinting of polymeric hydrogels","volume":"16","author":"GhavamiNejad","year":"2020","journal-title":"Small"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/adem.200700220","article-title":"Temporal assembly of collagen type II studied by atomic force microscopy","volume":"9","author":"Dong","year":"2007","journal-title":"Adv. Eng. Mater."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8707","DOI":"10.1039\/C7TB02348K","article-title":"Photo-crosslinked mono-component type II collagen hydrogel as a matrix to induce chondrogenic differentiation of bone marrow mesenchymal stem cells","volume":"5","author":"Yang","year":"2017","journal-title":"J. Mater. Chem. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1002\/jbm.a.36731","article-title":"Glyoxal cross-linking of solubilized extracellular matrix to produce highly porous, elastic, and chondro-permissive scaffolds for orthopedic tissue engineering","volume":"107","author":"Browe","year":"2019","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31036","DOI":"10.1038\/srep31036","article-title":"Precise tuning of facile one-pot gelatin methacryloyl (GelMA) synthesis","volume":"6","author":"Shirahama","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.biomaterials.2009.09.073","article-title":"Concentrated collagen hydrogels as dermal substitutes","volume":"31","author":"Helary","year":"2010","journal-title":"Biomaterials"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1089\/ten.tea.2015.0513","article-title":"Effects of composition and mechanical property of injectable collagen I\/II composite hydrogels on chondrocyte behaviors","volume":"22","author":"Yuan","year":"2016","journal-title":"Tissue Eng. Part A"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1021\/bm0257412","article-title":"Photo-cross-linking of type I collagen gels in the presence of smooth muscle cells: Mechanical properties, cell viability, and function","volume":"4","author":"Brinkman","year":"2003","journal-title":"Biomacromolecules"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.foodchem.2007.09.022","article-title":"Purification and characterization of type II collagen from chick sternal cartilage","volume":"108","author":"Cao","year":"2008","journal-title":"Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"044107","DOI":"10.1088\/1758-5090\/aa8dd8","article-title":"Proposal to assess printability of bioinks for extrusion-based bioprinting and evaluation of rheological properties governing bioprintability","volume":"9","author":"Paxton","year":"2017","journal-title":"Biofabrication"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/2\/216\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:08:41Z","timestamp":1760134121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/2\/216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,27]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["biom12020216"],"URL":"https:\/\/doi.org\/10.3390\/biom12020216","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,27]]}}}