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The balance of oxidative stress and the coupling of vessel and bone ingrowth are critical for bone regeneration. In this study, an injectable heterogeneous silk gel scaffold which can spatiotemporally and sustainedly release bone mesenchymal stem cell\u2010derived small extracellular vesicles, HIF\u20101<jats:italic>\u03b1<\/jats:italic> pathway activator, and inhibitor is developed for bone repair and vertebral reinforcement. The initial enhancement of HIF\u20101<jats:italic>\u03b1<\/jats:italic> upregulates the expression of VEGF to promote angiogenesis, and the balance of reactive oxygen species level is regulated to effectively eliminate oxidative damage and abnormal microenvironment. The subsequent inhibition of HIF\u20101<jats:italic>\u03b1<\/jats:italic> avoids the overexpression of VEGF and vascular overgrowth. Meanwhile, complex macroporous structures and suitable mechanical support can be obtained within the silk gel scaffolds, which will promote in situ bone regeneration. 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