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In this study, by integrating silver nanoclusters (AgNCs) and M2 macrophage\u2010derived extracellular vesicles (M2EVs), a multifunctional DNA\u2010based hydrogel, called Agevgel, is developed with antibacterial, anti\u2010inflammatory, immunomodulatory, and osteogenic properties to promote DABD rebuilding. AgNCs are tightly embedded into the DNA scaffolds and exhibit effective anti\u2010bacterial activity, while immunomodulatory M2EVs are encapsulated within the shape\u2010variable DNA scaffolds and exhibit potent anti\u2010inflammatory and osteogenic properties. The results reveal that Agevgel effectively prolongs the local retention time and bioactivity of M2EVs in vivo. In particular, the sustained release of M2EVs can last for at least 7 days when applying Agevgel to DABD. Compared to free M2EVs or Aggel (AgNCs encapsulated within the DNA hydrogel) treatments, the Agevgel treatment accelerates the defect healing rate of alveolar bone and dramatically improves the trabecular architecture. Mechanistically, Agevgel plays a key role in regulating macrophage polarization and promoting the expression of proliferative and osteogenic factors. In summary, Agevgel provides a comprehensive treatment strategy for DABD with a great clinical translational value, highlighting the application of DNA hydrogels as an ideal bioscaffolds for periodontal diseases.<\/jats:p>","DOI":"10.1002\/smll.202305594","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T04:50:55Z","timestamp":1698987055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Multifunctional DNA\u2010Based Hydrogel Promotes Diabetic Alveolar Bone Defect Reconstruction"],"prefix":"10.1002","volume":"20","author":[{"given":"Ge","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism West China Hospital Sichuan University Chengdu 610041 China"},{"name":"Center for Diabetes and Metabolism Research West China Hospital Sichuan University Chengdu 610041 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