{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:56:29Z","timestamp":1790445389152,"version":"4.1.0"},"reference-count":88,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Graphene\u2010based materials (GBMs) hold strong promise to restore the spinal cord microenvironment and promote functional recovery after spinal cord injury (SCI). Nanocomposites consisting of reduced graphene oxide (rGO) and adipose tissue\u2010derived extracellular matrix (adECM) are known to promote neuronal growth in vitro and to evoke a biocompatible response in vivo when implanted on top of the intact spinal cord. In this study, pristine adECM and adECM\u2010rGO nanocomposites are implanted directly after hemisection SCI in rats. Scaffolds composed of collagen type I (COL) are applied as negative control, based on evidence that COL triggers integrin\u2010mediated astrogliosis. However, COL scaffolds induce orthotopic bone formation in the lesion site and are therefore excluded from further analyses. Compared to pristine adECM, adECM\u2010rGO nanocomposites completely restore spinal cord integrity. Macrophage\u2010mediated uptake and clearance of rGO remnants is observed as early as 3 weeks post\u2010implantation. Nanocomposites show an elevated presence of \u03b2III\u2010tubulin\u2010positive axons in the host\u2010material interface after 8 weeks, yet scaffold penetration by axons is only occasionally observed. This is partially due to an increased expression of chondroitin sulfate proteoglycans (CSPGs) within the nanocomposites, even though reactive astrogliosis is unaltered. Despite the complete restoration of tissue architecture, adECM\u2010rGO treatment does not significantly improve functional recovery.<\/jats:p>","DOI":"10.1002\/adhm.202402775","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T23:56:49Z","timestamp":1734047809000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Application of Adipose Extracellular Matrix and Reduced Graphene Oxide Nanocomposites for Spinal Cord Injury Repair"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5116-123X","authenticated-orcid":false,"given":"Kest","family":"Verstappen","sequence":"first","affiliation":[{"name":"Department of Dentistry\u2010Regenerative Biomaterials Radboud University Medical Center  Nijmegen 6525 EX The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Bieler","sequence":"additional","affiliation":[{"name":"Institute of Experimental Neuroregeneration Paracelsus Medical University  Salzburg 5020 Austria"},{"name":"Austrian Cluster for Tissue Regeneration  Vienna 1200 Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Barroca","sequence":"additional","affiliation":[{"name":"Centre for Mechanical Technology and Automation (TEMA) Intelligent Systems Associate Laboratory (LASI) Department of Mechanical Engineering University of Aveiro  Aveiro 3810\u2010193 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewald M.","family":"Bronkhorst","sequence":"additional","affiliation":[{"name":"Department of Dentistry\u2010Regenerative Biomaterials Radboud University Medical Center  Nijmegen 6525 EX The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Couillard\u2010Despr\u00e9s","sequence":"additional","affiliation":[{"name":"Institute of Experimental Neuroregeneration Paracelsus Medical University  Salzburg 5020 Austria"},{"name":"Austrian Cluster for Tissue Regeneration  Vienna 1200 Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1471-6133","authenticated-orcid":false,"given":"Sander C.G.","family":"Leeuwenburgh","sequence":"additional","affiliation":[{"name":"Department of Dentistry\u2010Regenerative Biomaterials Radboud University Medical Center  Nijmegen 6525 EX The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula A.A.P.","family":"Marques","sequence":"additional","affiliation":[{"name":"Centre for Mechanical Technology and Automation (TEMA) Intelligent Systems Associate Laboratory (LASI) Department of Mechanical Engineering University of Aveiro  Aveiro 3810\u2010193 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Klymov","sequence":"additional","affiliation":[{"name":"Department of Dentistry\u2010Regenerative Biomaterials Radboud University Medical Center  Nijmegen 6525 EX The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5742-9826","authenticated-orcid":false,"given":"X. Frank","family":"Walboomers","sequence":"additional","affiliation":[{"name":"Department of Dentistry\u2010Regenerative Biomaterials Radboud University Medical Center  Nijmegen 6525 EX The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41393-020-00582-5"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sc.2015.133"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00282"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2009.08.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.18"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201601130"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0475-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1227\/neu.0000000000001932"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6TB00152A"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c04756"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn5066028"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2023.213653"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3tb21085e"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbon.2013.03.010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2018-0269"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201500333"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4103\/2152-7806.182964"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.05.012"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.11.024"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.0c00345"},{"key":"e_1_2_9_21_1","first-page":"651","volume":"47","author":"Pan S.","year":"2019","journal-title":"Artif. Cells, Nanomed. Biotechnol."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.306095"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1RA00861G"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2022.212971"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114506"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.11.012"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.10.005"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2015.0422"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2017.0089"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.4c00067"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13233-014-2135-5"},{"key":"e_1_2_9_32_1","author":"Kim J. H.","year":"2018","journal-title":"Stem Cells Int."},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22083847"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200307068"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.114877"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.09.053"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2024.213794"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2023.213351"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101059"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4354"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3NR03145D"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810625"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbon.2014.09.044"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113273"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2021.0194"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.4061\/2010\/650857"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.06.016"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3171\/2009.4.SPINE08784"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.06.019"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00188"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-38558-y"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-018-0083-8"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.8b00658"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201200489"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.0c03438"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx200339h"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.11.012"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9020143"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197233"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/clr.13133"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202207224"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.11.002"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00795-015-0104-5"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.851542"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121689"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.04.021"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041086"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matdes.2020.109092"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.01.038"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368913X674657"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67526-0"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.11.027"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202300123"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2023.213385"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.9b01557"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.09.001"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.01.024"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b04609"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201200846"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3nr02161k"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4TB00668B"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2014.12.027"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbon.2015.06.079"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.05.024"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.2826"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1995.12.1"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202402775","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T21:12:31Z","timestamp":1759785151000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202402775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,12]]},"references-count":88,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/adhm.202402775"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202402775","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,12]]},"assertion":[{"value":"2024-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2402775"}}