{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:06:52Z","timestamp":1791821212622,"version":"4.3.4"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Acta Biomaterialia"],"published-print":{"date-parts":[[2018,3]]},"DOI":"10.1016\/j.actbio.2018.01.025","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T10:46:34Z","timestamp":1517395594000},"page":"83-94","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":65,"special_numbering":"C","title":["Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo"],"prefix":"10.1016","volume":"69","author":[{"given":"Melika","family":"Sarem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Arya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Heizmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel T.","family":"Neffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Barbero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim P.","family":"Gebauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Lendlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. Prasad","family":"Shastri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"12","key":"10.1016\/j.actbio.2018.01.025_b0005","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.2106\/00004623-199812000-00011","article-title":"The healing and regeneration of articular cartilage","volume":"80","author":"O'Driscoll","year":"1998","journal-title":"J. Bone Joint Surg. Am."},{"key":"10.1016\/j.actbio.2018.01.025_b0010","doi-asserted-by":"crossref","unstructured":"S.N. Redman, S.F. Oldfield, C.W. Archer, Current strategies for articular cartilage repair, Eur. Cell Mater. 9(1) (2005) 23\u201332; discussion 23\u201332.","DOI":"10.22203\/eCM.v009a04"},{"issue":"3","key":"10.1016\/j.actbio.2018.01.025_b0015","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":"Steinert","year":"2007","journal-title":"Arthritis Res. Ther."},{"issue":"9940","key":"10.1016\/j.actbio.2018.01.025_b0020","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0140-6736(14)60544-4","article-title":"Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial","volume":"384","author":"Fulco","year":"2014","journal-title":"Lancet"},{"issue":"10055","key":"10.1016\/j.actbio.2018.01.025_b0025","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1016\/S0140-6736(16)31658-0","article-title":"Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial","volume":"388","author":"Mumme","year":"2016","journal-title":"Lancet"},{"issue":"32-33","key":"10.1016\/j.actbio.2018.01.025_b0030","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1002\/adma.200900608","article-title":"In vivo engineering of tissues: biological considerations, challenges, strategies, and future directions","volume":"21","author":"Shastri","year":"2009","journal-title":"Adv. Mater."},{"issue":"4","key":"10.1016\/j.actbio.2018.01.025_b0035","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1021\/mp100437a","article-title":"Biomaterial-mediated delivery of microenvironmental cues for repair and regeneration of articular cartilage","volume":"8","author":"Toh","year":"2011","journal-title":"Mol. Pharm."},{"issue":"5","key":"10.1016\/j.actbio.2018.01.025_b0040","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/term.169","article-title":"Comparative chondrogenesis of human cell sources in 3D scaffolds","volume":"3","author":"Seda Tigli","year":"2009","journal-title":"J. Tissue Eng. Regen. Med."},{"issue":"5","key":"10.1016\/j.actbio.2018.01.025_b0045","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1089\/ten.2006.12.1345","article-title":"Effects of cross-linking type II collagen-GAG scaffolds on chondrogenesis in vitro: dynamic pore reduction promotes cartilage formation","volume":"12","author":"Vickers","year":"2006","journal-title":"Tissue Eng."},{"issue":"43","key":"10.1016\/j.actbio.2018.01.025_b0050","doi-asserted-by":"crossref","first-page":"5971","DOI":"10.1039\/c3tb20680g","article-title":"Collagen grafted 3D polycaprolactone scaffolds for enhanced cartilage regeneration","volume":"1","author":"Cai","year":"2013","journal-title":"J. Mater. Chem. B"},{"issue":"10","key":"10.1016\/j.actbio.2018.01.025_b0055","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/term.375","article-title":"3D ingrowth of bovine articular chondrocytes in biodegradable cryogel scaffolds for cartilage tissue engineering","volume":"5","author":"Bolgen","year":"2011","journal-title":"J. Tissue Eng. Regen. Med."},{"issue":"5","key":"10.1016\/j.actbio.2018.01.025_b0060","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s13346-012-0080-4","article-title":"Substrate elasticity modulates TGF beta stimulated re-differentiation of expanded human articular chondrocytes","volume":"2","author":"Vonwil","year":"2012","journal-title":"Drug. Deliv. Transl. Res."},{"issue":"2","key":"10.1016\/j.actbio.2018.01.025_b0065","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/jbm.b.33011","article-title":"Collagen hydrogel as an immunomodulatory scaffold in cartilage tissue engineering","volume":"102","author":"Yuan","year":"2014","journal-title":"J. Biomed. Mater. Res. Part B-Appl. Biomater."},{"issue":"3","key":"10.1016\/j.actbio.2018.01.025_b0070","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/jbm.a.10443","article-title":"Biosynthetic response of passaged chondrocytes in a type II collagen scaffold to mechanical compression","volume":"64","author":"Lee","year":"2003","journal-title":"J. Biomed. Mater. Res. A"},{"issue":"2","key":"10.1016\/j.actbio.2018.01.025_b0075","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/jbm.b.30096","article-title":"Antigenicity and immunogenicity of collagen","volume":"71","author":"Lynn","year":"2004","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"10.1016\/j.actbio.2018.01.025_b0080","doi-asserted-by":"crossref","unstructured":"S. Gorgieva, V. Kokol, Collagen-vs. gelatine-based biomaterials and their biocompatibility: review and perspectives, in: R. Pignatello (Ed.), Biomaterials Applications for Nanomedicine, 2011, pp. 17\u201358.","DOI":"10.5772\/24118"},{"issue":"7","key":"10.1016\/j.actbio.2018.01.025_b0085","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1021\/bm900036s","article-title":"Evaluation of cross-linking methods for electrospun gelatin on cell growth and viability","volume":"10","author":"Sisson","year":"2009","journal-title":"Biomacromolecules"},{"issue":"2","key":"10.1016\/j.actbio.2018.01.025_b0090","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.carbpol.2012.11.099","article-title":"How can genipin assist gelatin\/carbohydrate chitosan scaffolds to act as replacements of load-bearing soft tissues?","volume":"93","author":"Sarem","year":"2013","journal-title":"Carbohydr. Polym."},{"issue":"8","key":"10.1016\/j.actbio.2018.01.025_b0095","doi-asserted-by":"crossref","first-page":"4777","DOI":"10.1016\/j.msec.2013.07.036","article-title":"Optimization strategies on the structural modeling of gelatin\/chitosan scaffolds to mimic human meniscus tissue","volume":"33","author":"Sarem","year":"2013","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"issue":"6","key":"10.1016\/j.actbio.2018.01.025_b0100","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1021\/bm500241y","article-title":"Gelatin-based biomaterial engineering with anhydride-containing oligomeric cross-linkers","volume":"15","author":"Loth","year":"2014","journal-title":"Biomacromolecules"},{"issue":"4","key":"10.1016\/j.actbio.2018.01.025_b0105","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1021\/bm050013a","article-title":"Oxidized chondroitin sulfate-cross-linked gelatin matrixes: a new class of hydrogels","volume":"6","author":"Dawlee","year":"2005","journal-title":"Biomacromolecules"},{"key":"10.1016\/j.actbio.2018.01.025_b0110","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.2147\/IJN.S28753","article-title":"Nanoscale modification of porous gelatin scaffolds with chondroitin sulfate for corneal stromal tissue engineering","volume":"7","author":"Lai","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.actbio.2018.01.025_b0115","doi-asserted-by":"crossref","unstructured":"C.W. Yung, L.Q. Wu, J.A. Tullman, G.F. Payne, W.E. Bentley, T.A. Barbari, Transglutaminase crosslinked gelatin as a tissue engineering scaffold, J. Biomed. Mater. Res. Part A 83a(4) (2007) 1039\u20131046.","DOI":"10.1002\/jbm.a.31431"},{"key":"10.1016\/j.actbio.2018.01.025_b0120","doi-asserted-by":"crossref","unstructured":"A.T. Neffe, B.F. Pierce, G. Tronci, N. Ma, E. Pittermann, T. Gebauer, O. Frank, M. Schossig, X. Xu, B.M. Willie, M. Forner, A. Ellinghaus, J. Lienau, G.N. Duda, A. Lendlein, One step creation of multifunctional 3D architectured hydrogels inducing bone regeneration, Adv. Mater. 27(10) (2015) 1738\u20131744.","DOI":"10.1002\/adma.201404787"},{"issue":"32","key":"10.1016\/j.actbio.2018.01.025_b0125","doi-asserted-by":"crossref","first-page":"12887","DOI":"10.1073\/pnas.1222880110","article-title":"Polysaccharide hydrogels with tunable stiffness and provasculogenic properties via alpha-helix to beta-sheet switch in secondary structure","volume":"110","author":"Forget","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"8","key":"10.1016\/j.actbio.2018.01.025_b0130","doi-asserted-by":"crossref","first-page":"7640","DOI":"10.1016\/j.actbio.2013.04.050","article-title":"Stiffness and adhesivity control aortic valve interstitial cell behavior within hyaluronic acid based hydrogels","volume":"9","author":"Duan","year":"2013","journal-title":"Acta Biomater"},{"issue":"15","key":"10.1016\/j.actbio.2018.01.025_b0135","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1016\/j.biomaterials.2012.01.065","article-title":"Modulation of mesenchymal stem cell chondrogenesis in a tunable hyaluronic acid hydrogel microenvironment","volume":"33","author":"Toh","year":"2012","journal-title":"Biomaterials"},{"issue":"18","key":"10.1016\/j.actbio.2018.01.025_b0140","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.1091\/mbc.e12-03-0172","article-title":"ECM stiffness primes the TGF beta pathway to promote chondrocyte differentiation","volume":"23","author":"Allen","year":"2012","journal-title":"Mol. Biol. Cell"},{"issue":"1","key":"10.1016\/j.actbio.2018.01.025_b0145","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0003-2697(92)90513-7","article-title":"The determination of \u220a-amino groups in soluble and poorly soluble proteinaceous materials by a spectrophotometrie method using trinitrobenzenesulfonic acid","volume":"207","author":"Bubnis","year":"1992","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.actbio.2018.01.025_b0150","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.actbio.2017.05.021","article-title":"Direct quantification of dual protein adsorption dynamics in three dimensional systems in presence of cells","volume":"57","author":"Sarem","year":"2017","journal-title":"Acta Biomater."},{"issue":"77","key":"10.1016\/j.actbio.2018.01.025_b0155","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.1098\/rsif.2012.0564","article-title":"Recapitulating tumour microenvironment in chitosan-gelatin three-dimensional scaffolds: an improved in vitro tumour model","volume":"9","author":"Arya","year":"2012","journal-title":"J. R. Soc. Interface"},{"issue":"8","key":"10.1016\/j.actbio.2018.01.025_b0160","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1016\/j.biomaterials.2005.08.035","article-title":"A comparison of micro CT with other techniques used in the characterization of scaffolds","volume":"27","author":"Ho","year":"2006","journal-title":"Biomaterials"},{"issue":"1","key":"10.1016\/j.actbio.2018.01.025_b0165","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/0003-2697(88)90532-5","article-title":"Fluorometric Assay of DNA in Cartilage Explants Using Hoechst-33258","volume":"174","author":"Kim","year":"1988","journal-title":"Anal. Biochem."},{"issue":"2","key":"10.1016\/j.actbio.2018.01.025_b0170","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.ydbio.2007.06.003","article-title":"MMP-2 functions as a negative regulator of chondrogenic cell condensation via down-regulation of the FAK-integrin beta1 interaction","volume":"308","author":"Jin","year":"2007","journal-title":"Dev. Biol."},{"issue":"8","key":"10.1016\/j.actbio.2018.01.025_b0175","doi-asserted-by":"crossref","first-page":"3418","DOI":"10.1073\/pnas.0907774107","article-title":"Autologous engineering of cartilage","volume":"107","author":"Emans","year":"2010","journal-title":"P. Natl. Acad. Sci. USA"},{"issue":"2","key":"10.1016\/j.actbio.2018.01.025_b0185","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1677\/joe.0.1650457","article-title":"The distribution of stanniocalcin 1 protein in fetal mouse tissues suggests a role in bone and muscle development","volume":"165","author":"Jiang","year":"2000","journal-title":"J. Endocrinol."},{"issue":"1","key":"10.1016\/j.actbio.2018.01.025_b0190","doi-asserted-by":"crossref","first-page":"R26","DOI":"10.1186\/ar1873","article-title":"Degradation of small leucine-rich repeat proteoglycans by matrix metalloprotease-13: identification of a new biglycan cleavage site","volume":"8","author":"Monfort","year":"2006","journal-title":"Arthritis Res. Ther."},{"issue":"1","key":"10.1016\/j.actbio.2018.01.025_b0195","first-page":"39","article-title":"Matrix metalloproteinases: What do they not do? New substrates and biological roles identified by murine models and proteomics","volume":"1803","author":"Rodriguez","year":"2010","journal-title":", Bba-Mol. Cell Res."},{"issue":"1","key":"10.1016\/j.actbio.2018.01.025_b0200","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S0014-4827(05)80067-9","article-title":"Cell condensation in chondrogenic differentiation","volume":"200","author":"Tacchetti","year":"1992","journal-title":"Exp. Cell Res."},{"issue":"Pt 16","key":"10.1016\/j.actbio.2018.01.025_b0205","first-page":"3703","article-title":"Fibronectin and stem cell differentiation - lessons from chondrogenesis","volume":"125","author":"Singh","year":"2012","journal-title":"J. Cell Sci."},{"issue":"5","key":"10.1016\/j.actbio.2018.01.025_b0210","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1053\/joca.1999.0306","article-title":"Cellular interactions and signaling in cartilage development","volume":"8","author":"DeLise","year":"2000","journal-title":"Osteoarthritis Cartil."},{"key":"10.1016\/j.actbio.2018.01.025_b0215","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.actbio.2015.05.023","article-title":"Combinatorial effect of substratum properties on mesenchymal stem cell sheet engineering and subsequent multi-lineage differentiation","volume":"23","author":"Chuah","year":"2015","journal-title":"Acta Biomater"},{"issue":"5611","key":"10.1016\/j.actbio.2018.01.025_b0220","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/267531a0","article-title":"Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture","volume":"267","author":"Von Der Mark","year":"1977","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.actbio.2018.01.025_b0225","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0014-5793(83)80592-4","article-title":"Collagen of fibrocartilage: a distinctive molecular phenotype in bovine meniscus","volume":"158","author":"Eyre","year":"1983","journal-title":"FEBS Lett."},{"issue":"5","key":"10.1016\/j.actbio.2018.01.025_b0230","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ceb.2004.07.010","article-title":"Regulation of matrix biology by matrix metalloproteinases","volume":"16","author":"Mott","year":"2004","journal-title":"Curr. Opin. Cell. Biol."},{"issue":"1","key":"10.1016\/j.actbio.2018.01.025_b0235","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1172\/JCI116547","article-title":"Expression of 92-kD type IV collagenase\/gelatinase (gelatinase B) in osteoarthritic cartilage and its induction in normal human articular cartilage by interleukin 1","volume":"92","author":"Mohtai","year":"1993","journal-title":"J. Clin. Invest."},{"issue":"1","key":"10.1016\/j.actbio.2018.01.025_b0240","first-page":"245","article-title":"Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage","volume":"151","author":"Imai","year":"1997","journal-title":"Am. J. Pathol."},{"issue":"7","key":"10.1016\/j.actbio.2018.01.025_b0245","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1034\/j.1600-0714.2000.290705.x","article-title":"Expression of matrix metalloproteinase-2 in osteoarthritic fibrocartilage from human mandibular condyle","volume":"29","author":"Tanaka","year":"2000","journal-title":"J. Oral Pathol. Med."},{"issue":"1","key":"10.1016\/j.actbio.2018.01.025_b0250","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/bit.10352","article-title":"Determination of oxygen gradients in engineered tissue using a fluorescent sensor","volume":"80","author":"Kellner","year":"2002","journal-title":"Biotechnol. Bioeng."},{"issue":"1","key":"10.1016\/j.actbio.2018.01.025_b0255","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1053\/joca.2001.0477","article-title":"Redifferentiation of dedifferentiated bovine articular chondrocytes in alginate culture under low oxygen tension","volume":"10","author":"Domm","year":"2002","journal-title":"Osteoarthritis Cartil."},{"issue":"5","key":"10.1016\/j.actbio.2018.01.025_b0260","doi-asserted-by":"crossref","DOI":"10.1088\/1468-6996\/14\/5\/054403","article-title":"A comparative study of the chondrogenic potential between synthetic and natural scaffolds in an in vivo bioreactor","volume":"14","author":"Huang","year":"2013","journal-title":"Sci. Technol. Adv. Mat."}],"container-title":["Acta Biomaterialia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1742706118300369?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1742706118300369?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:01:46Z","timestamp":1761670906000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1742706118300369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3]]},"references-count":51,"alternative-id":["S1742706118300369"],"URL":"https:\/\/doi.org\/10.1016\/j.actbio.2018.01.025","relation":{},"ISSN":["1742-7061"],"issn-type":[{"value":"1742-7061","type":"print"}],"subject":[],"published":{"date-parts":[[2018,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo","name":"articletitle","label":"Article Title"},{"value":"Acta Biomaterialia","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.actbio.2018.01.025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}