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To address this clinical challenge, a dual\u2010function bioactive scaffolds is developed that simultaneously blocks disease progression and promotes tissue regeneration. The scaffolds design incorporates three key components: First, MnO<jats:sub>2<\/jats:sub>\u2010Cu<jats:sup>2+<\/jats:sup> (MC) nanoparticles are synthesized to combat the pathological microenvironment through dual mechanisms of ROS scavenging and angiogenesis promotion. Second, circular bone morphogenetic protein 2 (circBMP2) is engineered for sustained BMP2 expression to enhance osteogenic differentiation, with polyethylenimine\u2010mediated surface conjugation onto MC nanoparticles. Finally, these MC\u2010circBMP2 (MCB) complexes are integrated into a dopamine\u2010modified demineralized bone matrix scaffolds to create a hierarchically structured regenerative platform. In vivo experiments showed that the bioactive scaffolds promoted the healing of atrophic nonunion of radial bone defects in rabbits by improving angiogenesis, scavenging ROS, and accelerating the osteogenic differentiation of endogenous cells. The above results indicate that the designed bioactive scaffolds can precisely block the pathology and rapidly initiate the regeneration of damaged tissue, providing theoretical guidance for the regeneration of pathological refractory tissue injuries.<\/jats:p>","DOI":"10.1002\/adhm.202500120","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T01:38:13Z","timestamp":1745804293000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Treatment of Large Bone Defects with Atrophic Nonunion by Bioactive Scaffolds Remodeling the Regeneration Microenvironment"],"prefix":"10.1002","volume":"14","author":[{"given":"Zhuo","family":"Liang","sequence":"first","affiliation":[{"name":"Clinical Medical Center of Tissue Engineering and Regeneration Institutes of Health Central Plain The Third Affiliated Hospital of Xinxiang Medical University Xinxiang Medical University  Xinxiang 453003 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