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Intervertebral disc (IVD) degeneration (IVDD) has been considered the dominant factor in low back pain (LBP), and its etiological mechanisms are complex and not yet fully elucidated. To date, the treatment of IVDD has mainly focused on relieving clinical symptoms and cannot fundamentally solve the problem. Recently, a novel microsphere-based therapeutic strategy has held promise for IVD regeneration and has yielded encouraging results with in vitro experiments and animal models. With excellent injectability, biocompatibility, and biodegradability, this microsphere carrier allows for targeted delivery and controlled release of drugs, gene regulatory sequences, and other bioactive substances and supports cell implantation and directed differentiation, aiming to improve the disease state of IVD at the source. This review discusses the possible mechanisms of IVDD and the limitations of current therapies, focusing on the application of microsphere delivery systems in IVDD, including targeted delivery of active substances and drugs, cellular therapy, and gene therapy, and attempts to provide a new understanding for the treatment of IVDD.

Abstract Background Spinal cord injury (SCI) is a devastating disease, which results in tissue loss and neurologic dysfunction. NLRP3 inflammasome plays an important role in the mechanism of diverse diseases. However, no studies have demonstrated the role of NLRP3 inflammasome and the effects of NLRP3 inflammasome inhibitors in a mouse model of SCI. We investigated whether inhibition of NLRP3 inflammasome activation by the pharmacologic inhibitor BAY 11-7082 or A438079 could exert neuroprotective effects in a mouse model of SCI. Methods SCI was performed using an aneurysm clip with a closing force of 30 g at the level of the T6-T7 vertebra for 1 min. Motor recovery was evaluated by an open-field test. Neuronal death was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining. Mitochondrial dysfunction was determined by quantitative real-time polymerase chain reaction (qPCR), western blot, and detection of mitochondrial membrane potential level. Microglia/macrophage activation and astrocytic response were evaluated by immunofluorescence labeling. Results Inhibition of NLRP3 inflammasome activation by pharmacologic inhibitor BAY 11-7082 or A438079 reduced neuronal death, attenuated spinal cord anatomic damage, and promoted motor recovery. Furthermore, BAY 11-7082 or A438079 directly attenuated the levels of NLRP3 inflammasome and proinflammatory cytokines. Moreover, BAY 11-7082 or A438079 alleviated microglia/macrophage activation, neutrophils infiltration, and reactive gliosis, as well as mitochondrial dysfunction. Conclusions Collectively, our results demonstrate that pharmacologic suppression of NLRP3 inflammasome activation controls neuroinflammation, attenuates mitochondrial dysfunction, alleviates the severity of spinal cord damage, and improves neurological recovery after SCI. These data strongly indicate that the NLRP3 inflammasome is a vital contributor to the secondary damage of SCI in mice.