{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:05:04Z","timestamp":1792739104905,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M761834"],"award-info":[{"award-number":["2024M761834"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010029","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["tsqnz20221168"],"award-info":[{"award-number":["tsqnz20221168"]}],"id":[{"id":"10.13039\/501100010029","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":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinal cord injury (SCI), a highly disabling injury to the central nervous system, has a complex and sequential pathogenesis. Traditional multiple\u2010delivery systems rely on a physical mix of nanoparticles or drugs in hydrogels, which lacks the controllability of the drug. To solve these problems, an integrative hydrogel system cross\u2010linked with a Per\u2010g\u2010PSB nanogel is designed. Dendritic macromolecular nanogels (Per\u2010g\u2010PSB) could not only act as cross\u2010linkers to adjust the hydrogel mechanical properties but also form a dynamic network (Dex\/Per\u2010g\u2010PSB hydrogel). Most importantly, a large amount of charge could lead to a significant sustained release via electrostatic interactions. The hydrogel platform (Mel\/Ibu@D\/P\u2010g\u2010PSB) realizes the sequential release of melatonin and ibuprofen by different mechanisms. Melatonin is first released by diffusion and exhibits significant neuroprotective effects during the acute phase by downregulating the expression of inflammatory cytokines. Ibuprofen is released in the second stage due to strong electrostatic interactions, and it reduces RhoA signaling activation by blocking the ROCK pathway in the subacute phase, which reduces the deleterious cascade reaction after spinal cord injury. These results show that the ion\u2010sensitive hydrogel platform with sequentially releasing drug effects, combining anti\u2010inflammatory effects and blocking the ROCK pathway, shows excellent repair of SCI.<\/jats:p>","DOI":"10.1002\/advs.202510976","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T10:16:11Z","timestamp":1762942571000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Nanogel Integrated Zwitterionic Injectable Hydrogel with Sequential Drug\u2010Releasing Capability for the Programmable Repair of Spinal Cord Injury"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhijian","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Qilu Hospital, Shandong University Centre for Orthopaedics Advanced Medical Research Institute Shandong University  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susu","family":"Huang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education) State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Department of Pharmaceutics School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University  No. 44 Wenhua West Road, Lixia District Jinan 250012 China"},{"name":"Department of Pharmacy Zhongshan Hospital Fudan University  180 Fenglin Road Shanghai 200032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Qilu Hospital, Shandong University Centre for Orthopaedics Advanced Medical Research Institute Shandong University  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayao","family":"Wen","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education) State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Department of Pharmaceutics School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University  No. 44 Wenhua West Road, Lixia District Jinan 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Qilu Hospital, Shandong University Centre for Orthopaedics Advanced Medical Research Institute Shandong University  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education) State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Department of Pharmaceutics School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University  No. 44 Wenhua West Road, Lixia District Jinan 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoye","family":"Yang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education) State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Department of Pharmaceutics School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University  No. 44 Wenhua West Road, Lixia District Jinan 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Hospital of Shandong University  No. 247 Beiyuan Street, Tianqiao District Jinan 250033 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxi","family":"Zhai","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education) State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Department of Pharmaceutics School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University  No. 44 Wenhua West Road, Lixia District Jinan 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Shi","sequence":"additional","affiliation":[{"name":"Neck\u2010Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University Shandong First Medical University &amp; Shandong Academy of Medical Sciences  No. 18877, Jingshi Road, Lixia District Jinan 518873 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7969-5308","authenticated-orcid":false,"given":"Lin","family":"Jin","sequence":"additional","affiliation":[{"name":"International Joint Research Laboratory for Biomedical Nanomaterials of Henan Zhoukou Normal University  No. 6, Middle Section of Wenchang Avenue, Chuanhui District Zhoukou 466001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dachuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Hospital of Shandong University  No. 247 Beiyuan Street, Tianqiao District Jinan 250033 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Qilu Hospital, Shandong University Centre for Orthopaedics Advanced Medical Research Institute Shandong University  Jinan Shandong 250012 China"},{"name":"Department of Orthopaedics The Second Hospital of Shandong University  No. 247 Beiyuan Street, Tianqiao District Jinan 250033 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ye","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education) State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Department of Pharmaceutics School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University  No. 44 Wenhua West Road, Lixia District Jinan 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0475-6"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11707-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05385-7"},{"key":"e_1_2_9_4_1","first-page":"16","volume":"5","author":"Ren H.","year":"2018","journal-title":"Adv. Sci."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0597-7"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.2927"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf2679"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa2958"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.037"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13974"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4541"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b01892"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.01.012"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202302286"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01669-2"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2022.120047"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121689"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0601-5"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics7030305"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201200175"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.2c21255"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202202510"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202101989"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00562-y"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02337-2"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05607-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3053"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-016-2122-7"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2010.00786.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12859"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202104773"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2021.147684"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.4684"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-00536-0"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwx057"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1308887110"},{"key":"e_1_2_9_37_1","first-page":"11","volume":"452","author":"Yu Q. N.","year":"2023","journal-title":"Chem. Eng. J."},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202313212"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202510976","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202510976","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202510976","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:46:06Z","timestamp":1775979966000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202510976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/advs.202510976"],"URL":"https:\/\/doi.org\/10.1002\/advs.202510976","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"assertion":[{"value":"2025-08-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10976"}}