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However, the need for repeated administration and the complex oral environment present challenges in balancing biosafety and efficiency. Herein, we develop a ligand\u2010modulated manganese ferrite nanozyme hydrogel (MFZ@PG) with balanced antioxidant activity and biocompatibility for periodontitis treatment through ZBP1\/\u03b2\u2010catenin signaling. MFZ@PG is synthesized by encapsulating zwitterionic dopamine sulfonate\u2010modified manganese ferrite nanoparticles within a gel matrix composed of polyvinyl alcohol, gelatin, and borax. The resulting hydrogel demonstrates potent antioxidant capacity, attributed to the innate nanozyme activity of manganese ferrite and the introduced catechol groups, as well as robust adhesiveness due to multiple chemical interactions between borax and polyvinyl alcohol. In vitro experiments demonstrate that MFZ@PG effectively protects MC3T3\u2010E1 cells from H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced impairment of proliferation, migration, and osteogenic differentiation. In vivo experiments demonstrate that MFZ@PG significantly promotes alveolar bone regeneration and suppresses bone resorption. Furthermore, transcriptomic analysis indicates that the therapeutic mechanism of MFZ@PG is achieved through the activation of the ZBP1\/\u03b2\u2010catenin positive feedback loop. Histopathological and blood biochemical analyses demonstrate the good biocompatibility of MFZ@PG. This study presents a safe and efficient therapeutic strategy for periodontitis with high translational potential.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202505568","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T10:49:51Z","timestamp":1770029391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ligand\u2010Modulated Manganese Ferrite Nanozyme Hydrogel with Balanced Antioxidant Activity and Biocompatibility for Periodontitis Treatment"],"prefix":"10.1002","volume":"15","author":[{"given":"Leyu","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"},{"name":"Department of Orthodontics Tianjin Medical University School and Hospital of Stomatology &amp; Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology the Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyue","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Tianjin Medical University School and Hospital of Stomatology &amp; Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bosha","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Tianjin Medical University School and Hospital of Stomatology &amp; Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Tianjin Medical University School and Hospital of Stomatology &amp; Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0801-8435","authenticated-orcid":false,"given":"Ruxia","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Rehabilitation Division of Medical Technology Tianjin Medical University  Tianjin China"},{"name":"Department of Physical Rehabilitation and Medicine Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6136-9969","authenticated-orcid":false,"given":"Shao\u2010Kai","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13506"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101849"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12342"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13769"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12430"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.14074"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00488-6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13245"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13259"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2025.125850"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12504"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101309"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.40917"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-024-00205-1"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586-024-00315-5"},{"key":"e_1_2_10_17_1","article-title":"Catalase\u2010Like Nanozymes: Classification, Catalytic Mechanisms, and Their Applications","volume":"18","author":"Xu D. 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