{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:20:10Z","timestamp":1788268810143,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Persistent inflammation, insufficient vascularization and impaired osteogenesis limit the repair of critical\u2010sized femoral defects. Although microRNA\u2010210\u20103p (miR\u2010210\u20103p) can regulate these processes, its therapeutic use is constrained by poor extracellular stability and inefficient cellular entry. Here, miR\u2010210\u20103p was incorporated into a tetrahedral framework nucleic acid (tFNA) to create tFNAs\u2010miR\u2010210\u20103p. Dynamic light scattering, zeta\u2010potential analysis, atomic force microscopy (AFM) and capillary electrophoresis supported formation of the negatively charged nanosystem. In RAW264.7 macrophages, tFNA delivery increased Cy5\u2010labelled miR\u2010210\u20103p\u2010positive cells from 1.24% for free miR\u2010210\u20103p to 99.93%. Under lipopolysaccharide (LPS)\u2010induced inflammatory conditions, tFNAs\u2010miR\u2010210\u20103p reduced CD86 and inducible nitric oxide synthase, increased CD206 and arginase\u20101, enhanced endothelial tube formation and improved osteogenic differentiation. It suppressed M1 marker CD86\/iNOS and elevated M2 marker CD206\/Arg\u20101 to resolve the inflammatory microenvironment. Mechanistically, miR\u2010210\u20103p directly binds the 3\u2032UTR of EFNA3 mRNA to inhibit its expression, thereby activating AKT\/STAT3 signalling to switch macrophages toward reparative phenotype. In a rat critical\u2010sized femoral defect model, local tFNAs\u2010miR\u2010210\u20103p treatment improved histological repair, macrophage polarisation, microcomputed\u2010tomography indices, vascularization and osteocalcin expression at 4 and 8\u2009weeks. These findings identify tFNA\u2010mediated miR\u2010210\u20103p delivery as a promising immunomodulatory strategy for vascularised bone regeneration.<\/jats:p>","DOI":"10.1111\/cpr.70277","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:45:15Z","timestamp":1788266715000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tetrahedral Framework Nucleic Acid Delivery of\n                    <scp>miR<\/scp>\n                    \u2010210\u20103p Promotes Femoral Bone Regeneration Through\n                    <scp>EFNA3<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>STAT3<\/scp>\n                    \u2010Mediated Immunomodulation"],"prefix":"10.1111","author":[{"given":"Lei","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The First Affiliated Hospital of Nanjing Medical University  Nanjing China"},{"name":"Department of Orthopedics Sichuan Lansheng Brain Hospital and Shanghai Lansheng Brain Hospital Investment Co. Ltd.  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5591-9426","authenticated-orcid":false,"given":"Kaixiao","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-3719","authenticated-orcid":false,"given":"Jiahu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7511-3582","authenticated-orcid":false,"given":"Weitong","family":"Cui","sequence":"additional","affiliation":[{"name":"Psychiatric Laboratory and Mental Health Center, The State Key Laboratory of Biotherapy West China Hospital of Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.10.019"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046\u20103758.97.BJR\u20102019\u20100289.R2"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.02.020"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5TB00593K"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S432509"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2024.10.027"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbon.2026.121651"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202505714"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202509727"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202518814"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.74889"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c12917"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123183"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368\u2010024\u201000298\u20103"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.06.003"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800731200"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2846"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.2414336"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010024\u201001046\u2010z"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010020\u20100355\u20100"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.2107820"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010022\u201000212\u20101"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010022\u201000791\u20107"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202109728"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202109609"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202308701"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.2202513"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368\u2010024\u201000315\u20103"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2022.134855"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010026\u201000530\u20108"}],"container-title":["Cell 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