{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T19:54:27Z","timestamp":1784404467741,"version":"3.55.0"},"reference-count":81,"publisher":"Wiley","issue":"27","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Long bone fractures are primarily repaired through endochondral ossification, where a soft cartilage template forms at the injury site and is gradually replaced by bone. While bone has an innate self\u2010healing capacity, this process can fail in cases of large or complex defects, requiring clinical intervention. We developed a tissue engineering approach using human periosteum\u2010derived cell (hPDC) spheroids encapsulated or bioprinted at high density within hyaluronic acid methacrylate (HAMA) hydrogels to support hypertrophic cartilage formation as a template relevant to endochondral bone regeneration. Encapsulation at different timepoints (days 1, 7, and 14) showed that early encapsulation enhanced spheroid interaction, increased DNA content, and promoted hypertrophic cartilage formation, with greater glycosaminoglycan (GAG) and collagen deposition, and\n                    <jats:italic>lacunae<\/jats:italic>\n                    formation. HAMA\u2010encapsulated spheroids were compared to spheroids formed using a standardized microwell platform, showing that encapsulation supported cartilage\u2010like matrix formation with collagen deposition, Safranin O\u2010positive extracellular matrix and\n                    <jats:italic>lacunae<\/jats:italic>\n                    , while maintaining progression toward a hypertrophic phenotype. Gene expression and immunostaining confirmed progression toward hypertrophic and osteogenic phenotypes. Finally, extrusion\u2010based bioprinting of HAMA containing a high density of hPDC spheroids demonstrated scalability while maintaining cell viability and hypertrophic differentiation, although precise spatial control over spheroid positioning remains to be optimized.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202505855","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T05:33:43Z","timestamp":1773639223000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Packed for Ossification: High\u2010Density Bioprinting of hPDC Spheroids in HAMA Toward Endochondral Ossification"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0596-402X","authenticated-orcid":false,"given":"Ane","family":"Albillos Sanchez","sequence":"first","affiliation":[{"name":"Complex Tissue Regeneration Department MERLN Institute for Technology\u2010Inspired Regenerative Medicine Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4869-5636","authenticated-orcid":false,"given":"Maria Paula","family":"Marks","sequence":"additional","affiliation":[{"name":"Department of Cell Biology\u2010Inspired Tissue Engineering MERLN Institute for Technology\u2010Inspired Regenerative Medicine Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0638-6456","authenticated-orcid":false,"given":"Paula","family":"Casademunt","sequence":"additional","affiliation":[{"name":"Physense, BCN Medtech Department of Engineering Universitat Pompeu Fabra  Physense Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8950-367X","authenticated-orcid":false,"given":"Adri\u00e1n","family":"Seijas\u2010Gamardo","sequence":"additional","affiliation":[{"name":"Complex Tissue Regeneration Department MERLN Institute for Technology\u2010Inspired Regenerative Medicine Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4754-5492","authenticated-orcid":false,"given":"Ioannis","family":"Papantoniou","sequence":"additional","affiliation":[{"name":"Prometheus Division of Skeletal Tissue Engineering KU Leuven  Leuven Belgium"},{"name":"Department of Development and Regeneration Skeletal Biology and Engineering Research Center KU Leuven  Leuven Belgium"},{"name":"Institute of Chemical Engineering Sciences Foundation For Research and Technology\u2010Hellas  Patras Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1298-6025","authenticated-orcid":false,"given":"Lorenzo","family":"Moroni","sequence":"additional","affiliation":[{"name":"Complex Tissue Regeneration Department MERLN Institute for Technology\u2010Inspired Regenerative Medicine Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5935-6245","authenticated-orcid":false,"given":"Carlos","family":"Mota","sequence":"additional","affiliation":[{"name":"Complex Tissue Regeneration Department MERLN Institute for Technology\u2010Inspired Regenerative Medicine Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925\u20104773(99)00142\u20102"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2011.03.031"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.1"},{"issue":"4","key":"e_1_2_11_5_1","article-title":"Nonunion in Patients With Tibial Shaft Fractures: Is Early Physical Status Associated With Fracture Healing?","volume":"12","author":"Mundi R.","year":"2020","journal-title":"Cureus"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-9-66"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0000000000001420"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031128"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1185841"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevBiomedEng.v40.i5.10"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.03.016"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.11.012"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086\u2010199810001\u201000003"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v015a05"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105370"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2022.0115"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1235992"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v6.i3.266"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201003124\u2010z"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1292483"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010006\u20100308\u2010z"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14111133"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.01.005"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345231205273"},{"issue":"2","key":"e_1_2_11_25_1","article-title":"Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing","volume":"7","author":"Hall G. N.","year":"2020","journal-title":"Advancement of Science"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.10.037"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.120820"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10468"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fceng.2022.892190"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202413680"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2008.12.084"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2023.0198"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121881"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.10.169"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122243"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0281345"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758\u20105090\/adb2e6"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582\u20104934.2009.00807.x"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2015.0436"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20104165(86)90306\u20105"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v12.i2.110"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.12.001"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-021-00133-3"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202408032"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202313776"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2018.00062"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1177\/19476035231154530"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/ac2208"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521\u20101878(200002)22:2<138::AID\u2010BIES5>3.0.CO;2\u20104"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.946992"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/gels9120925"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.09.052"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.03.010"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.20568"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650110604"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep36011"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szad091"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24439"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.08.007"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.601224"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.11.145"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2018.0237"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.202000401"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.01.047"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.109.2.327"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010018\u20100021\u2010z"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774\u2010011\u20100273\u20109"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23115974"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.337063"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvs004"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24045"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.683939"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008208909002412"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2024.108132"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.1918"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000302107"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42242-024-00273-7"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/admt.202500210"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758\u20105090\/ad6e1a"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw5111"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758\u20105090\/abc1bf"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201021029\u20102"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202505855","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202505855","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202505855","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:51:31Z","timestamp":1784296291000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202505855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,15]]},"references-count":81,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/adhm.202505855"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202505855","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,15]]},"assertion":[{"value":"2025-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e05855"}}