{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:39Z","timestamp":1785428079742,"version":"3.56.0"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Research Fund of Zhejiang Provincial Multi-omics and Molecular Enzymology Key Laboratory, Yangtze Delta Region Institute of Tsinghua University, Zhejiang","award":["2025YB004"],"award-info":[{"award-number":["2025YB004"]}]},{"award":["2025YB004"],"award-info":[{"award-number":["2025YB004"]}],"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Key Laboratory of Multi-omics and Molecular Enzymology","award":["2024E10101"],"award-info":[{"award-number":["2024E10101"]}]},{"name":"Beijing\u2013Tianjin\u2013Hebei Basic Research Cooperation Project","award":["J230012"],"award-info":[{"award-number":["J230012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The current lack of effective treatments for traumatic spinal cord injury (SCI) presents a significant challenge in managing the complex microenvironmental alterations that follow the initial trauma. This study developed an injectable alginate hydrogel dynamically cross-linked by tannic acid\u2013zinc nanoparticles (TA@Zn NPs), which exerts neuroprotective effects through the sustained release of zinc ions (Zn2+) and antioxidant TA@Zn NPs. TA@Zn NPs were cross-linked with phenylboronic acid-modified sodium alginate (SA) to form an injectable gel system. In response to the acidic and ROS-rich microenvironment characteristic of SCI, the hydrogel undergoes degradation, thereby triggering the disintegration of TA@Zn NPs and the concomitant release of Zn2+, enabling sustained therapeutic delivery. In a rat model of contusion injury, the degradation of TA@Zn NPs and the sustained release of Zn2+ significantly reduced oxidative damage and promoted axonal regeneration, which in turn inhibited scar formation and enhanced the tissue\u2019s antioxidant capacity. Consequently, the group treated with the Zn2+-releasing hydrogel exhibited significant recovery of motor function. Collectively, these results validate the dual-function integration of Zn2+ as a dynamic cross-linker and neuroprotective agent within injectable hydrogels as a robust strategy for SCI repair, presenting a clinically translatable paradigm for neural regeneration.<\/jats:p>","DOI":"10.3390\/md24050176","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:46:55Z","timestamp":1778676415000},"page":"176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sodium Alginate Hydrogel with Zinc Ion Nanoparticles for Synergistic Neuroprotection and Functional Recovery in Spinal Cord Injury"],"prefix":"10.3390","volume":"24","author":[{"given":"Chuanxi","family":"Chi","sequence":"first","affiliation":[{"name":"School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao 266113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianshun","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao 266113, China"},{"name":"College of Chemical and Biological Engineering, Shandong University of Science and Technology, Qingdao 266590, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Han","sequence":"additional","affiliation":[{"name":"School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao 266113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao 266113, China"},{"name":"Institute of Neurobiology, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilong","family":"Cao","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-4027","authenticated-orcid":false,"given":"Liming","family":"Li","sequence":"additional","affiliation":[{"name":"School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao 266113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41413-022-00199-9","article-title":"Progression in translational research on spinal cord injury based on microenvironment imbalance","volume":"10","author":"Fan","year":"2022","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101378","DOI":"10.1016\/j.mtbio.2024.101378","article-title":"Hyaluronidase-responsive hydrogel loaded with magnetic nanoparticles combined with external magnetic stimulation for spinal cord injury repair","volume":"30","author":"Fan","year":"2024","journal-title":"Mater. Today Bio"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Duan, P., Wang, D., Zhang, H., Kang, S., and Lin, Z. (2026). Orchestrating Scarless Spinal Cord Repair: Dynamic Glial-Immune Interplay and Biomaterial Support. Adv. Healthc. Mater., e03952.","DOI":"10.1002\/adhm.202503952"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e18097","DOI":"10.1002\/adfm.202518097","article-title":"Dual-Pathway Modulated Biomimetic Conductive Hydrogel Conduit Enables Spatiotemporal Co-Delivery of Engineered C3-Exosomes and TT-10 to Potentiate Optic Nerve Regeneration","volume":"36","author":"Sun","year":"2025","journal-title":"Adv. Funct. Mater."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"171115","DOI":"10.1016\/j.cej.2025.171115","article-title":"Reactive oxygen species-scavenging, overloaded calcium-inhibiting, neuroregeneration-promoting polydopamine functionalized magnesium oxide nanoparticle-integrated hydrogel accelerates spinal cord injury repair","volume":"526","author":"Wei","year":"2025","journal-title":"Chem. Eng. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"52346","DOI":"10.1021\/acsami.1c14679","article-title":"Antioxidative and Conductive Nanoparticles-Embedded Cell Niche for Neural Differentiation and Spinal Cord Injury Repair","volume":"13","author":"Wu","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gu, J., Yuan, H., Chu, B., Wang, T., Fan, J., Shi, F., Wu, J., Sun, X., and Feng, X. (2025). A ROS-scavenging peptide hydrogel combined with mesenchymal stem cells for promoting spinal cord injury recovery. Chin. Chem. Lett., 112123.","DOI":"10.1016\/j.cclet.2025.112123"},{"key":"ref_8","first-page":"13","article-title":"Developmental phases of Neurorestoratology and current key tasks","volume":"2","author":"Huang","year":"2025","journal-title":"J. Neurorestoratol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"012002","DOI":"10.1088\/2057-1976\/ab52e8","article-title":"In situ injectable hydrogels for spinal cord regeneration: Advances from the last 10 years","volume":"6","author":"Morgado","year":"2019","journal-title":"Biomed. Phys. Eng. Express"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102514","DOI":"10.1016\/j.mtbio.2025.102514","article-title":"Application of injectable hydrogels in the central and peripheral nervous system as a unique and flexible platform for neural tissue repair","volume":"35","author":"Wu","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Abka-khajouei, R., Tounsi, L., Shahabi, N., Patel, A.K., Abdelkafi, S., and Michaud, P. (2022). Structures, Properties and Applications of Alginates. Mar. Drugs, 20.","DOI":"10.3390\/md20060364"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chejara, D., Mabrouk, M., Kumar, P., Choonara, Y., Kondiah, P., Badhe, R., Toit, L., Bijukumar, D., and Pillay, V. (2017). Synthesis and Evaluation of a Sodium Alginate-4-Aminosalicylic Acid Based Microporous Hydrogel for Potential Viscosupplementation for Joint Injuries and Arthritis-Induced Conditions. Mar. Drugs, 15.","DOI":"10.3390\/md15080257"},{"key":"ref_13","first-page":"173","article-title":"Current frontier technologies in spinal cord injury research: A narrative review","volume":"2","author":"Zhong","year":"2025","journal-title":"Adv. Technol. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Li, D., Bai, M., Guo, Z., Cui, Y., Mei, X., Tian, H., and Shen, Z. (2025). Zinc regulates microglial polarization and inflammation through IKB\u03b1 after spinal cord injury and promotes neuronal repair and motor function recovery in mice. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1510372"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1021\/acsnano.3c10541","article-title":"Engineered Multifunctional Zinc\u2013Organic Framework-Based Aggregation-Induced Emission Nanozyme for Accelerating Spinal Cord Injury Recovery","volume":"18","author":"Zheng","year":"2024","journal-title":"ACS Nano"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12951-024-03018-x","article-title":"A cryo-shocked M2 macrophages based treatment strategy promoting repair of spinal cord injury via immunomodulation and axonal regeneration effects","volume":"23","author":"Lu","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.4103\/NRR.NRR-D-24-01677","article-title":"Exercise training promotes nerve cell repair and regeneration after spinal cord injury","volume":"21","author":"Zhai","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1007\/s11837-025-07330-1","article-title":"Synergistic Effects of Magnesium and Zinc Ions on Neural Stem Cell Proliferation and Differentiation","volume":"77","author":"Kim","year":"2025","journal-title":"JOM"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wu, H., Feng, X., Mei, Z., Huang, W., and Liu, Y. (2026). Preparation and Characterization of Double-Network Composite Hydrogels with Carboxymethyl Pachymaran in Promoting Wound Healing. Foods, 15.","DOI":"10.3390\/foods15081285"},{"key":"ref_20","first-page":"e01262","article-title":"An eco-friendly, sodium alginate degradable conformal triboelectric nanogenerator for self-powered sensing and real-time injury monitoring","volume":"43","author":"Feng","year":"2025","journal-title":"Sustain. Mater. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.ijbiomac.2021.09.123","article-title":"Effect of tannic acid on the mechanical and adhesive properties of catechol-modified hyaluronic acid hydrogels","volume":"191","author":"Gwak","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Michalska-Sionkowska, M., War\u017cy\u0144ska, O., Kaczmarek-Szczepa\u0144ska, B., \u0141ukowicz, K., Osyczka, A.M., and Walczak, M. (2021). Characterization of Collagen\/Beta Glucan Hydrogels Crosslinked with Tannic Acid. Polymers, 13.","DOI":"10.3390\/polym13193412"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1800234","DOI":"10.1002\/macp.201800234","article-title":"Tannic Acid Physically Cross-Linked Responsive Hydrogel","volume":"219","author":"Zheng","year":"2018","journal-title":"Macromol. Chem. Phys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s10904-018-0963-z","article-title":"The Effect of RF Power on the Properties of Gallium and Aluminium Co-doped Zinc Oxide (GAZO) Thin Films","volume":"29","author":"Muchuweni","year":"2018","journal-title":"J. Inorg. Organomet. Polym. Mater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102006","DOI":"10.1016\/j.mtbio.2025.102006","article-title":"Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineering","volume":"33","author":"Guo","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.matlet.2017.05.099","article-title":"One-step method to construct hydroxyapatite scaffolds with 3-D interconnected structure by a novel hydrogel bead porogen process","volume":"203","author":"Shi","year":"2017","journal-title":"Mater. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1016\/j.cell.2018.10.043","article-title":"Mechanisms for Zinc and Proton Inhibition of the GluN1\/GluN2A NMDA Receptor","volume":"175","author":"Chowdhury","year":"2018","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2306203","DOI":"10.1002\/advs.202306203","article-title":"Nanoenabled Intracellular Metal Ion Homeostasis Regulation for Tumor Therapy","volume":"11","author":"Xu","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eadx7035","DOI":"10.1126\/sciadv.adx7035","article-title":"CysMP reveals metal ion\u2013specific metalloproteomes and copper-regulated PGK1 activity in glycolysis","volume":"11","author":"Yuan","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e70040","DOI":"10.1002\/btm2.70040","article-title":"Enhancement of spinal cord injury repair in rats using photo-crosslinked GelMA hydrogel combined with mitochondrial transplantation","volume":"10","author":"Gao","year":"2025","journal-title":"Bioeng. Transl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.7150\/thno.26717","article-title":"Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair","volume":"8","author":"Wang","year":"2018","journal-title":"Theranostics"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/5\/176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:54:59Z","timestamp":1778835299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/5\/176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["md24050176"],"URL":"https:\/\/doi.org\/10.3390\/md24050176","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]}}}