{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:23:20Z","timestamp":1780086200810,"version":"3.54.0"},"reference-count":65,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Low back pain is the leading cause of disability worldwide, but current therapeutic interventions are palliative or surgical in nature. Loss of notochordal cells (NCs) and degradation of the healthy matrix in the nucleus pulposus (NP), the central tissue of intervertebral discs (IVDs), has been associated with onset of degenerative disc changes. Recently, we established a protocol for decellularization of notochordal cell derived matrix (NCM) and found that it can provide regenerative cues to nucleus pulposus cells of the IVD. Here, we combined the biologically regenerative properties of decellularized NCM with the mechanical tunability of a poly(ethylene glycol) hydrogel to additionally address biomechanics in the degenerate IVD. We further introduced a hydrolysable PEG\u2010diurethane crosslinker for slow degradation of the gels in vivo<jats:italic>.<\/jats:italic> The resulting hydrogels were tunable over a broad range of stiffness's (0.2 to 4.5\u2009kPa), matching that of NC\u2010rich and \u2010poor NP tissues, respectively. Gels formed within 30\u2009min, giving ample time for handling, and remained shear\u2010thinning post\u2010polymerization. Gels also slowly released dNCM over 28\u2009days as measured by GAG effusion. Viability of encapsulated bone marrow stromal cells after extrusion through a needle remained high. Although encapsulated NCs stayed viable over two\u2009weeks, their metabolic activity decreased, and their phenotype was lost in physiological medium conditions in vitro. Overall, the obtained gels hold promise for application in degenerated IVDs but require further tuning for combined use with NCs.<\/jats:p>","DOI":"10.1002\/jbm.a.37594","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T09:50:20Z","timestamp":1691142620000},"page":"1903-1915","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Semi\u2010synthetic degradable notochordal cell\u2010derived matrix hydrogel for use in degenerated intervertebral discs: Initial in vitro characterization"],"prefix":"10.1002","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4247-1620","authenticated-orcid":false,"given":"Tara C.","family":"Schmitz","sequence":"first","affiliation":[{"name":"Orthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-4469","authenticated-orcid":false,"given":"Bas","family":"van Genabeek","sequence":"additional","affiliation":[{"name":"SyMO\u2010Chem BV  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten J.","family":"Pouderoijen","sequence":"additional","affiliation":[{"name":"SyMO\u2010Chem BV  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk M.","family":"Janssen","sequence":"additional","affiliation":[{"name":"SyMO\u2010Chem BV  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"van Doeselaar","sequence":"additional","affiliation":[{"name":"Orthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6818-6401","authenticated-orcid":false,"given":"Jo\u00e3o F.","family":"Crispim","sequence":"additional","affiliation":[{"name":"Orthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-7162","authenticated-orcid":false,"given":"Marianna A.","family":"Tryfonidou","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences of Companion Animals Faculty of Veterinary Medicine, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7372-4072","authenticated-orcid":false,"given":"Keita","family":"Ito","sequence":"additional","affiliation":[{"name":"Orthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)30970\u20109"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092200402"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.01.013"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v008a06"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.11.009"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2021.0226"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2018.0026"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25476"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.2c00790"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2020.08.001"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.02.029"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm100137q"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.202000085"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709885200"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics10020055"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.5b00420"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00311"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21483"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0040\u20108166(82)90033\u20107"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201001567\u2010w"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2226"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ily015"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7538025"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584\u2010020\u201000568\u2010w"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027170"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1028"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1027"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104471\u20105451\u20108_109"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2006.10.019"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1175"},{"key":"e_1_2_11_32_1","unstructured":"U.S. Department of Health and Human Services; Food and Drug Administration.Content and review of chemistry manufacturing and control (CMC) information for human somatic cell therapy investigational new drug applications (INDs). Guidance for FDA reviewers and sponsors 2008 1\u201336."},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12195\u2010011\u20100164\u20100"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2019.05.120"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15030371"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021143516436"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000192236.92867.15"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100150224"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken396"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2014.07.013"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.polymdegradstab.2006.05.019"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.polymdegradstab.2012.04.008"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym14091672"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30607"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3293"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA04320H"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1088\/0957\u20104484\/20\/36\/365602"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1089\/107632704323061870"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.06.061"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.02.023"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1039\/c8sm01066h"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.3109\/17453676908989482"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.26434\/chemrxiv.8971136.v1"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.201400379"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actamat.2012.10.037"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/ma9508616"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v032a11"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202100596"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00402\u2010014\u20102097\u20102"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v040a15"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.780749"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632\u2010200405150\u201000010"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2013.0479"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9020509"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.100"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.35243"}],"container-title":["Journal of Biomedical Materials Research Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.37594","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T04:53:32Z","timestamp":1696222412000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.a.37594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":65,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/jbm.a.37594"],"URL":"https:\/\/doi.org\/10.1002\/jbm.a.37594","archive":["Portico"],"relation":{},"ISSN":["1549-3296","1552-4965"],"issn-type":[{"value":"1549-3296","type":"print"},{"value":"1552-4965","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]},"assertion":[{"value":"2023-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}