Sustained gene delivery from inflammation-responsive anti-inflammatory hydrogels promotes extracellular matrix metabolism balance in degenerative nucleus pulposus

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.