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Proposed mechanism of healing CSDs over time: (A) Critical sized defect; (B) Endothelial Cells and Mesenchymal Stem Cells arrive in bone defect; (C) Antioxidant activity (NRF2, SOD1, GPX, CAT); (D) Angiogenic transcription markers expressed (HIF, ANG1, VEGF); (E) Vascular tubule formation; (F) Osteogenic transcription (RUNX2, OSX); (G) Collagen matrix formation; (H) Bone matrix protein synthesis (ALP, COL, OCN); (I) Bone formation; (J) Healed CSDs.
