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Cu2+-chelated epigallocatechin gallate nanoparticle-functionalized hydrogel promotes osteogenesis by inhibiting ferroptosis - PubMed

3 hours ago
  • #ferroptosis-inhibition
  • #bone-regeneration
  • #hydrogel-therapy
  • Cu2+-chelated epigallocatechin gallate nanoparticle-functionalized hydrogel (GGBH@EAC) promotes osteogenesis by inhibiting ferroptosis.
  • The hydrogel features EGCG-Arg-Cu (EAC) nanoparticles and nano-hydroxyapatite (nHAp) within a dual-network system of gelatin methacryloyl (GelMA), cationic guar gum (CG), and borax.
  • EAC inhibits ferroptosis by reprogramming lipid metabolism and restoring redox homeostasis, while nHAp provides essential minerals for bone regeneration.
  • The hydrogel is ROS-responsive, enabling controlled nanoparticle release under high-ROS conditions.
  • In vitro, GGBH@EAC scavenged ROS, alleviated mitochondrial damage, and promoted monounsaturated fatty acid synthesis, enhancing BMSC osteogenic differentiation.
  • Multi-omics analysis revealed the effects were mediated by SCD1-driven lipid metabolic reprogramming and downregulation of NOX1 and CYP.
  • In a rat bone defect model, GGBH@EAC achieved near-complete bone repair and vascularization within 8 weeks without systemic toxicity.
  • This work provides a translational platform to direct cellular metabolic fate against stress-induced death, unlocking bone regeneration.