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Here, to achieve sustained hypoxia manipulation, constructed hypoxia\u2010inducible interpenetrating polymer network (IPN) hydrogel microspheres (HIMS) are constructed by microfluidics to integrate the hypoxic system with a stabilizing network. The IPN is synthesized through a two\u2010step polymerization process, consisting of rapid photo\u2010crosslinked gelatin methacrylate anhydride (GM) polymer I and slow enzyme\u2010crosslinked vanillin\u2010grafted gelatin (GV) polymer II. The enzymatic reaction between GV and laccase is able to create a hypoxic microenvironment to modulate oxygen tension in situ within the injured region. HIMS can reduce microenvironmental oxygen tension by 1\/3 and maintain a hypoxic microenvironment for up to 5\u00a0days, thereby activating the PI3K\/AKT\/HIF\u20101\u03b1 signaling pathway in endogenous stem cells to promote differentiation into nucleus pulposus\u2010like cells. Additionally, NSC\u2010Exos are loaded onto HIMS to trigger endogenous progenitor\/stem cell recruitment and migration. Both in vitro and in vivo assays demonstrate that NSC\u2010Exos@HIMS facilitates stem cell recruitment, targets differentiation, and stimulates extracellular matrix synthesis. Overall, the microspheres established herein provide a novel strategy for manipulating oxygen tension and enhancing endogenous tissue regeneration in injured regions during intervertebral disc degeneration.<\/jats:p>","DOI":"10.1002\/advs.202417570","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T08:41:36Z","timestamp":1744706496000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Manipulation of Oxygen Tension in Damaged Regions via Hypoxia\u2010Induced IPN Hydrogel Microspheres for Intervertebral Disc Regeneration"],"prefix":"10.1002","volume":"12","author":[{"given":"Xingdie","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Spine Surgery Renji Hospital Shanghai Jiao Tong University School of Medicine  160 Pujian Road Shanghai 200127 P. R. 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