A hydrogel-based drug delivery system reduces inflammation and oxidative stress to alleviate intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a major cause of low back pain and spinal diseases, characterized by aberrant oxidative stress and inflammation in the affected disc tissues. Celecoxib is the most commonly used drug to treat IDD with significant anti-oxidation and anti-inflammation capacity. However, the poor blood supply of the intervertebral disc (IVD) restricts the bioavailability of celecoxib following oral administration. To address this issue, a hydrogel-based drug delivery system (HPPC) was developed by modifying hyaluronic acid (HA) with adipic dihydrazide (ADH) and 3-aminobenzeneboronic acid (PBA), aldehyde-functionalized polyethylene glycol (PEG-FBA), and celecoxib-loaded polydopamine (CLX@PDA) nanoparticles via dynamic Schiff base and boronic ester ligation. HPPC readily responds to high levels of reactive oxygen species (ROS) and low pH of the degenerated IVD microenvironment, enabling on-demand and sustainable celecoxib release. HPPC also possesses good mechanical properties, degradability, injectability and biocompatibility. In vivo and in vitro studies show the HPPC effectively reduces inflammation and oxidative stress in nucleus pulposus cells (NPCs) and restores disc function in IDD rats by regulating the COX2-PGE2-NFκB and TNFα-P38-MAPK pathways. This hydrogel drug delivery system offers a strategy for improving IDD treatment. STATEMENT OF SIGNIFICANCE: A dynamic hydrogel based on biopolymeric components (HPPC) is developed for treating intervertebral disc degeneration (IDD), which could respond to biochemical cues in degenerated discs to trigger on-demand celecoxib release. The HPPC treatment enables cooperative regulation of NF-κB and MAPK signaling activities in nucleus pulposus cells, which effectively reduces locogerional inflammation and oxidative stress to restore disc structure and function. This study offers an approach for improving IDD treatment in the clinic.