An anti-senescence hydrogel with pH-responsive drug release for mitigating intervertebral disc degeneration and low back pain.

ABSTRACT

Oxidative stress and aging lead to progressive senescence of nucleus pulposus (NP) cells, resulting in intervertebral disc (IVD) degeneration (IVDD). In some cases, degenerative IVD can further cause low back pain (LBP). Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD. However, the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs. Here, we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with quercetin to alleviate IVDD by removing senescent NP cells. The hydrogel exhibited injectability, biodegradability, prominent biocompatibility and responsive release of quercetin under pathological conditions. In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells. In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models, indicating a potential therapeutic approach for ameliorating IVDD and LBP. This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD, providing a new strategy for IVDD treatment.