Repair of degenerative nucleus pulposus by polyphenol nanosphere-encapsulated hydrogel gene delivery system

Intervertebral disc degeneration (IDD) progresses due to local inflammatory response, gradually unbalanced anabolic/catabolic activity, and progressive functional impairment within the nucleus pulposus. Antagomir-21, a cholesterol-modified miRNA-21 inhibitor, has potential extracellular matrix (ECM) regenerative ability, but its application for IDD is limited by inadequate local delivery systems. An injectable hydrogel gene delivery system encapsulating a modified tannic acid nanoparticles (TA NPs) vector was engineered for on-demand and sustained delivery of antagomir-21 into the nucleus pulposus. After nucleus pulposus cell uptake, antagomir-21 was released from TA NPs and regulated the ECM metabolic balance by inhibiting the MAPK/ERK signaling pathway. TA NPs scavenged intracellular ROS and reduced inflammation by downregulating TNF-α expression. In vivo, synergistic anti-inflammatory effects and ECM regeneration effectively promoted therapeutic efficacy against IDD. This hydrogel gene delivery system represents a creative, promising strategy for IDD repair.