Injectable chitosan microspheres resisting inflammatory and oxidative stress for ameliorating intervertebral disc degeneration

Abstract

The treatment of intervertebral disc (IVD) degeneration remains a significant challenge due to the unique ischemic structure of the IVD, which comprises the scavenging of inflammatory cytokines, alleviation of cellular oxidative stress responses, restoration of nuclei pulposus (NP) cell viability, and recovery of IVD biomechanical function. Herein, we developed an injectable microsphere (CS-MnO₂@PC) by incorporating chitosan microspheres (CS) with manganese dioxide (MnO₂) nanozymes and celecoxib encapsulated in Pluronic F-127 (PC) nanosized micelles, via in situ redox or Schiff base reaction. The hybrid carrier demonstrates robust capabilities in scavenging free radicals, alleviating extracellular oxidative stress, and reducing inflammatory cytokines in NP cells, as evidenced by RT-qPCR and immuno-fluorescence staining assays. In vivo evaluations further indicate that this hybrid carrier helps preserve NP hydration and the lamellar structure of the annulus fibrosus (AF), as confirmed by radiological analysis and histological staining evaluations. These injectable chitosan microspheres, combining nanozymes and nanosized drug micelles, represent a promising therapeutic strategy for degenerative IVD.