{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:13:52Z","timestamp":1789038832901,"version":"build-2803163510"},"reference-count":74,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"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":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This study presents the development of nanocomposite hydrogels that integrate functionalized reduced graphene oxide (rGO) derivatives carboxylated (CBX) and aminated (AMN) in combination with gellan gum, gelatin, and cellulose nanofibrils (CNFs) to enhance osteogenesis for bone tissue engineering. Their synthesis involves ultrasound exfoliation, genipin crosslinking, and freeze\u2010drying. Micro\u2010computed tomography (\u00b5CT) reveals highly porous, interconnected architectures facilitating nutrient diffusion and cell infiltration. CBX\/AMN scaffolds exhibit superior hydration capacity and a biphasic degradation profile. Spectroscopically, enhanced interfacial interactions were confirmed, contributing to the overall structural stability of the hydrogels. In vitro, all scaffolds are cytocompatible, sustain cell viability, and promote osteogenic differentiation consistent with adaptive cellmaterial interactions. Subcutaneous implantation in mice confirms scaffold biocompatibility, showing no signs of inflammation or foreign body response. Histological and immunofluorescence analyses reveal osteogenic potential, with enhanced mineralization and elevated expression of osteopontin and osteocalcin. \u00b5CT imaging of explants quantifies ectopic mineralization, spatial deposition patterns, and bone mineral density, correlating scaffold architecture and composition with osteogenic performance. These findings suggest that the synergistic integration of functionalized rGO, CNFs, and biopolymers results in scaffolds with enhanced structural and biological properties, highlighting their potential for design optimization and clinical translation in bone regenerative medicine.<\/jats:p>","DOI":"10.1002\/adhm.202501941","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T09:12:48Z","timestamp":1754557968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Functionalized Reduced Graphene Oxide\u2010Based Nanocomposite Hydrogels for Enhanced Osteogenesis in Bone Tissue Engineering"],"prefix":"10.1002","volume":"14","author":[{"given":"George Mihail","family":"Vl\u0103sceanu","sequence":"first","affiliation":[{"name":"Faculty of Medical Engineering National University of Science and Technology Politehnica Bucharest  Gheorghe Polizu 1\u20137 Bucharest 011061 Romania"},{"name":"Advanced Polymer Materials Group National University of Science and Technology Politehnica Bucharest  Gheorghe Polizu 1\u20137 Bucharest 011061 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u0103t\u0103lina Ionela","family":"Zamfir","sequence":"additional","affiliation":[{"name":"Faculty of Medical Engineering National University of Science and Technology Politehnica Bucharest  Gheorghe Polizu 1\u20137 Bucharest 011061 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornel","family":"Balt\u0103","sequence":"additional","affiliation":[{"name":"Aurel Ardelean Institute of Life Sciences Vasile Goldis Western University of Arad  94\u201396 Revolutiei Av. Arad 310025 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildegard","family":"Herman","sequence":"additional","affiliation":[{"name":"Aurel Ardelean Institute of Life Sciences Vasile Goldis Western University of Arad  94\u201396 Revolutiei Av. Arad 310025 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Ciceu","sequence":"additional","affiliation":[{"name":"Aurel Ardelean Institute of Life Sciences Vasile Goldis Western University of Arad  94\u201396 Revolutiei Av. Arad 310025 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Alexandra Duma","sequence":"additional","affiliation":[{"name":"Aurel Ardelean Institute of Life Sciences Vasile Goldis Western University of Arad  94\u201396 Revolutiei Av. Arad 310025 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9563-7148","authenticated-orcid":false,"given":"Mariana","family":"Ioni\u021b\u0103","sequence":"additional","affiliation":[{"name":"Faculty of Medical Engineering National University of Science and Technology Politehnica Bucharest  Gheorghe Polizu 1\u20137 Bucharest 011061 Romania"},{"name":"Advanced Polymer Materials Group National University of Science and Technology Politehnica Bucharest  Gheorghe Polizu 1\u20137 Bucharest 011061 Romania"},{"name":"eBio\u2010Hub Research Centre National University of Science and Technology Politehnica Bucharest\u2010Campus  Iuliu Maniu 6 Bucharest 061344 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana\u2010Cristina","family":"Popescu","sequence":"additional","affiliation":[{"name":"Faculty of Medical Engineering National University of Science and Technology Politehnica Bucharest  Gheorghe Polizu 1\u20137 Bucharest 011061 Romania"},{"name":"National Institute for Research and Development in Physics and Nuclear Engineering \u201cHoria Hulubei\u201d Department of Life and Environmental Physics  30 Reactor Magurele 007125 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Hermenean","sequence":"additional","affiliation":[{"name":"Aurel Ardelean Institute of Life Sciences Vasile Goldis Western University of Arad  94\u201396 Revolutiei Av. Arad 310025 Romania"},{"name":"Faculty of Medicine Vasile Goldis Western University of Arad  94\u201396 Revolutiei Av. Arad 310025 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15051334"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2023.12.010"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.5772\/61425"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e21872"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.734688"},{"key":"e_1_2_9_6_1","volume":"2","author":"Guo S.","year":"2020","journal-title":"Nanoscale Adv."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hybadv.2023.100070"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41428-020-0350-9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201500824"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.770049"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym15132762"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2023.121484"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/adem.202400247"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsanm.4c02701"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano13040772"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.36248"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/gels10040257"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpta.2023.100382"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148173"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.05.018"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.09.118"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym15102323"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.644595"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2024.122479"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2018.05.020"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1088\/1748-605X\/aa7f7b"},{"key":"e_1_2_9_27_1","volume":"5","author":"Chakraborty S.","year":"2018","journal-title":"R. Soc. Open Sci."},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2020.12.003"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202000631"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbon.2019.02.048"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2017.09.102"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.5772\/61909"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compositesb.2017.03.031"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr3000412"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121082"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2020.06.010"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032630"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105336"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/coatings10020189"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.12.031"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ma16051815"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e36258"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym16131827"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2RA07011A"},{"key":"e_1_2_9_45_1","first-page":"22","volume":"32","author":"Smith B.","year":"2017","journal-title":"The CO bond III, Ethers by a knockout"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2jm32479b"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2013.0638"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2021.112587"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1177\/20417314241282131"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rechem.2023.101029"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compositesa.2022.107235"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceramint.2022.05.080"},{"key":"e_1_2_9_53_1","first-page":"84","volume":"59","author":"Viprya P.","year":"2023","journal-title":"Eng. Proceed."},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano11071717"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303326"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevBiomedEng.v40.i5.10"},{"key":"e_1_2_9_57_1","first-page":"3631","volume":"5","author":"Liu M.","year":"2017","journal-title":"Bone Res."},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/ma8095273"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano10081444"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2023.100886"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202001414"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16599-5"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.07.010"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2013.05.026"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205077"},{"key":"e_1_2_9_66_1","first-page":"2249","volume":"24","author":"Dinescu S.","year":"2014","journal-title":"Biomed. Mater. Eng."},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.141804"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.614508"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.821288"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.70330"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-025-00417-0"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.3390\/jfb14030169"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-021-00180-y"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3RA02786D"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202501941","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202501941","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202501941","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T03:59:00Z","timestamp":1781755140000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202501941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,7]]},"references-count":74,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/adhm.202501941"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202501941","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,7]]},"assertion":[{"value":"2025-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01941"}}