Abstract
The progression of intervertebral disc degeneration (IDD) is characterized by an initial chronic local inflammatory response and ultimately leads to unbalanced anabolic/catabolic activity within the nucleus pulposus (NP). Injectable inflammation-responsive hydrogels have great potential in treating IDD through on-demand local drug delivery. Here, we designed an injectable inflammation-responsive gelatin-based hydrogel for local and sustained delivery of the naturally extracted anti-inflammatory curcumin and a cholesterol-modified miRNA-21 inhibitor (Antagomir-21) to treat IDD. We successfully demonstrated the robust biocompatibility and ideal inflammation-responsive and on-demand drug release properties of hydrogels, as well as the great potential of IDD regeneration. This work proposes the novel inflammation-responsive hydrogel-based curcumin and miRNA delivery systems for the treatment of IDD. • The hydrogel exhibited sensitve inflammation-responsive property (low pH and high ROS). • The on-demand delivered curcumin played strong anti-inflammatory role. • Cholesterol-modified miRNA would sustained release owing to the host-guest interactions with CD. • Antagomir-21 persistently promoted ECM regeneration of NPCs by promoting autophagy activation. • The anti-inflammation and ECM regeneration behavior of hydrogel positively promoted IDD repair.
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