{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:33:18Z","timestamp":1791315198976,"version":"4.3.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974333\/82172414"],"award-info":[{"award-number":["81974333\/82172414"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Corticosteroids\u2010induced Dickkopf\u20101 (DKK1) upregulation and Wnt signaling inhibition result in bone metabolism disorder and steroid\u2010associated osteonecrosis (SAON). Implanting biomaterials to regulate the Wnt pathway is a promising method to repair challenging bone defects associated with SAON. Here, tetrahedral DNA nanostructures (TDNs) are fabricated as gene carriers to deliver MiR335\u20105p, which targets DKK1 translation. Heparin lithium hydrogel (Li\u2010hep\u2010gel) is synthesized to act as a lithium and MiR@TDNs delivery agent. Finally, the repair effects on challenging bone defect in SAON using a MiR@TDNs\/Li\u2010hep\u2010gel composite are assessed in vivo. The results reveal that MiR@TDNs are absorbed by bone mesenchymal stem cells (BMSCs) and increase cell viability and reduce apoptosis. Moreover, MiR@TDNs promote alkaline phosphatase expression and calcium nodular deposition, decrease lipid droplet expression of BMSCs, and improve vascular endothelial growth factor secretion and vascular\u2010like structure formation in vitro. After MiR@TDNs\/Li\u2010hep\u2010gel is implanted into the SAON model, the internal bone defect of osteonecrosis is repaired with a large area of new bone accompanied with neovascularization and reduced empty lacunae. In conclusion, MiR@TDNs\/Li\u2010hep\u2010gel can provide dual delivery of lithium and MiR@TDNs, which synergistically upregulate the Wnt signaling pathway, enhancing bone regeneration in challenging bone defects, and can be potentially used in SAON repair.<\/jats:p>","DOI":"10.1002\/adhm.202101412","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T08:26:38Z","timestamp":1635150398000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Delivery of MiR335\u20105p\u2010Pendant Tetrahedron DNA Nanostructures Using an Injectable Heparin Lithium Hydrogel for Challenging Bone Defects in Steroid\u2010Associated Osteonecrosis"],"prefix":"10.1002","volume":"11","author":[{"given":"Donghai","family":"Li","sequence":"first","affiliation":[{"name":"Orthopedic Research Institution Department of Orthopaedics West China Hospital Sichuan University 37# Wuhou Guoxue Road Chengdu 610041 P. R. 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