{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:00:16Z","timestamp":1784761216899,"version":"3.55.0"},"reference-count":80,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001702","name":"AO Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001702","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Discogenic pain is associated with deep nerve ingrowth in annulus fibrosus tissue (AF) of intervertebral disc (IVD). To model AF nerve ingrowth, primary bovine dorsal root ganglion (DRG) micro\u2010scale tissue units are spatially organised around an AF explant by mild hydrodynamic forces within a collagen matrix. This results in a densely packed multicellular system mimicking the native DRG tissue morphology and a controlled AF\u2010neuron distance. Such a multicellular organisation is essential to evolve populational\u2010level cellular functions and in vivo\u2010like morphologies. Pro\u2010inflammatory cytokine\u2010primed AF demonstrates its neurotrophic and neurotropic effects on nociceptor axons. Both effects are dependent on the AF\u2010neuron distance underpinning the role of recapitulating inter\u2010tissue\/organ anatomical proximity when investigating their crosstalk. This is the first in vitro model studying AF nerve ingrowth by engineering mature and large animal tissues in a morphologically and physiologically relevant environment. The new approach can be used to biofabricate multi\u2010tissue\/organ models for untangling pathophysiological conditions and develop novel therapies.<\/jats:p>","DOI":"10.1002\/advs.202308478","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T14:16:27Z","timestamp":1702995387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-9832","authenticated-orcid":false,"given":"Junxuan","family":"Ma","sequence":"first","affiliation":[{"name":"AO Research Institute  Clavadelerstrasse 8 Davos 7270 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janick","family":"Eglauf","sequence":"additional","affiliation":[{"name":"AO Research Institute  Clavadelerstrasse 8 Davos 7270 Switzerland"},{"name":"ETH Z\u00fcrich  R\u00e4mistrasse 101 Z\u00fcrich 8092 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9552-3653","authenticated-orcid":false,"given":"Sibylle","family":"Grad","sequence":"additional","affiliation":[{"name":"AO Research Institute  Clavadelerstrasse 8 Davos 7270 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0262-1412","authenticated-orcid":false,"given":"Mauro","family":"Alini","sequence":"additional","affiliation":[{"name":"AO Research Institute  Clavadelerstrasse 8 Davos 7270 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5055-5117","authenticated-orcid":false,"given":"Tiziano","family":"Serra","sequence":"additional","affiliation":[{"name":"AO Research Institute  Clavadelerstrasse 8 Davos 7270 Switzerland"},{"name":"Complex Tissue Regeneration Department MERLN Institute for Technology\u2010Inspired Regenerative Medicine Maastricht University  Universiteitssingel 40 Maastricht 6229ET Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,19]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199806000-00028"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2741\/4280"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.80"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000201324.45537.46"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.87B1.15708"},{"key":"e_1_2_10_4_3","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200112010-00007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.08.026"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199910150-00002"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100120206"},{"key":"e_1_2_10_6_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)02135-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-809324-5.03129-1"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.021"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00271"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000219946.25103.db"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000000334"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-007-0414-y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13992"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201535"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0259-3"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-021-00279-y"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz5858"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-938-3_6"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.07.044"},{"key":"e_1_2_10_16_2","first-page":"1487","volume":"183","author":"Hanani M.","year":"2012","journal-title":"Brain Res."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2008.12.084"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-016-1704-5"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-2-28"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2021.100110"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/abbb9c"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201905713"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.07.110191.001001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.160"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0305"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1177\/1759091420974807"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12517"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2170-14.2015"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-7021(08)70088-9"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21725-z"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2011.02.012"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/admi.202100048"},{"key":"e_1_2_10_29_3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1121-09.2009"},{"key":"e_1_2_10_29_4","doi-asserted-by":"publisher","DOI":"10.1039\/C4LC00162A"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1121-09.2009"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-8-100"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.06.020"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408494102"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.08.015"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240000277"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-009-1760-2"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30925-9"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2010.01045.x"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.295341"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2014.00087"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2019.1665652"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909254107"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.35294"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1090"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06577.x"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.11.047"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.06.034"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v030a08"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2275"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-023-07672-x"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken056"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2015.11.019"},{"key":"e_1_2_10_50_1","author":"Wang D.","year":"2023","journal-title":"Spine J"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1014"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.80"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1512603113"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201804647"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr390"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189725"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1267"},{"key":"e_1_2_10_58_1","unstructured":"S.Andrews http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/2010."},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac958"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1000"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202308478","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T18:53:58Z","timestamp":1759776838000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202308478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,19]]},"references-count":80,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/advs.202308478"],"URL":"https:\/\/doi.org\/10.1002\/advs.202308478","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.01.30.526224","asserted-by":"object"}]},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,19]]},"assertion":[{"value":"2023-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2308478"}}