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A Dual-Strategy Hydrogel Targeting Glycolytic Reprogramming and Inflammation to Inhibit Ferroptosis and Promote Intervertebral Disc Repair - PubMed

6 hours ago
  • #hydrogel
  • #glycolysis
  • #ferroptosis
  • Intervertebral disc degeneration (IVDD) is a major cause of lower back pain, driven by metabolic changes like enhanced glycolysis.
  • Lactate, a glycolysis by-product, induces ferroptosis in nucleus pulposus cells (NPCs), worsening IVDD.
  • Inflammation enhances glycolysis and upregulates lactate dehydrogenase A (LDHA), creating a vicious cycle.
  • A dual-strategy hydrogel system was designed to target glycolytic reprogramming and inflammation.
  • The hydrogel uses PBA-functionalized G5 PAMAM to encapsulate LDHA siRNA, forming self-assembled nanoparticles (GPS).
  • GPS was modified with epigallocatechin (EGC) to form stable GPS-EGC nanoparticles via borate ester bonds.
  • The nanoparticles are incorporated into a ROS- and pH-responsive hydrogel for controlled drug release.
  • The system reduces IL-1β-induced inflammation and lactate production, alleviating ferroptosis in NPCs.
  • This approach promotes tissue repair in IVDD models, offering a promising therapeutic strategy.
  • The study highlights the potential of material innovation in modulating metabolic and inflammatory pathways.