Injectable hydrogel delivers targeted DEPTOR release, delaying intervertebral disc degeneration via inhibiting mTORC1 and further activating the PI3K/Akt pathway.

During intervertebral disc degeneration (IDD), apoptosis of nucleus pulposus cells (NPCs) exacerbates inflammatory responses, extracellular matrix degradation, and cell death, thereby accelerating the degenerative process. In this study, we found DEPTOR can delay IDD via inhibiting mTORC1 and further activating the PI3K/Akt pathway. So, we developed the oxidized sodium alginate (OSA)/CMCS@DEP hydrogel for sustained DEPTOR release in IDD treatment. This hydrogel features a dynamic network formed by Schiff base crosslinking between oxidized sodium alginate and carboxymethyl chitosan, offering excellent biocompatibility, injectability, and controlled degradability. The hydrogel permitted the efficient loading and sustained release of DEPTOR for targeted delivery. In a rat IDD model induced by puncture, the OSA/CMCS@DEP hydrogel significantly alleviated disc inflammation and slowed degenerative progression. These findings further confirmed that DEPTOR is a key therapeutic target for IDD, offering a novel treatment strategy for this condition.