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For local tissue injury with hypoxia, such as bone fracture and defects, a localized\u2010sufficient oxygen supply is highly desirable but remains challenging. Therefore, to explore a strategy and its intrinsic mechanism for supplying oxygen locally and remodeling the regenerative microenvironment, an innovative oxygenating hydrogel microsphere system with sustained oxygenation and antioxidant properties is introduced by loading CaO<jats:sub>2<\/jats:sub>@SiO<jats:sub>2<\/jats:sub>@PDA (CSP) nanoparticles. Specifically, the CSP nanoparticles exhibited broad\u2010spectrum free radicals scavenging ability, along with prolonged controlled\u2010release of oxygen once integrated into the gelatin methacrylate anhydride (GelMA) microspheres (CSP\u2010GM). The CSP\u2010GM with extra cellular matrix (ECM)\u2010mimicking structures reconstructed living niches, promoting the adhesion and proliferation of bone marrow stromal cells (BMSCs). As a multifaceted microenvironment regulator, CSP\u2010GM remodeled the regenerative microenvironment by synergistically producing oxygen and scavenging ROS, recovering mitochondrial homeostasis and antioxidant defenses of BMSCs, promoting angiogenesis and osteogenesis under hypoxia conditions via precisely modulating the Nrf2\/HO\u20101 signaling pathway. The multiple pro\u2010regenerative effects of the implantable functionalized micro\u2010oxygen reservoir on bone repair are further corroborated by the enhanced vascularized bone formation in rat femoral defects, presenting a comprehensive and promising strategy for tissue repair.<\/jats:p>","DOI":"10.1002\/advs.202409636","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T04:13:40Z","timestamp":1732594420000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Implantable Multifunctional Micro\u2010Oxygen Reservoir System for Promoting Vascular\u2010Osteogenesis via Remodeling Regenerative Microenvironment"],"prefix":"10.1002","volume":"12","author":[{"given":"Min","family":"Rui","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The First Affiliated Hospital of Soochow University Orthopaedic Institute of Soochow University  899 Pinghai Road Suzhou Jiangsu 215031 P. 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