Application of an Injectable Thermosensitive Hydrogel Drug Delivery System for Degenerated Intervertebral Disc Regeneration.

Abstract

Intervertebral disc degeneration is characterized by a localized, chronic inflammatory response leading to a synthesis/catabolism imbalance within the nucleus pulposus (NP) and progressive functional impairment within the NP. Polyphenol molecules have been widely used in anti-inflammatory therapies in recent years; therefore, we designed an injectable, temperature-sensitive hydrogel PLGA-PEG-PLGA-based drug delivery system for local and sustained delivery of two drugs tannic acid (TA) and resveratrol (Res), with the hydrogel carrying TA directly and Res indirectly (carried directly by inflammation-responsive nanoparticles). The delivery system presents good injectability at room temperature and forms a gel in situ upon entering the intervertebral disc. The delivery system can rapidly release TA and sustain Res release. In vitro and in vivo experiments have shown that this hydrogel drug delivery system is effective in anti-inflammation of degenerated intervertebral discs and promotes the regeneration of extracellular matrix in the NP.