pH-Responsive\nModified HAMA Microspheres Regulate\nthe Inflammatory Microenvironment of Intervertebral Discs

Currently, intervertebral\ndisc (IVD) degeneration is believed to\nlead to local accumulation of lactic acid in the IVD, a decrease in\npH, activation of the inflammatory pathway, and continued destruction\nof homeostasis of the IVD. To address these issues, the intelligent\nand accurate release of drugs is particularly important. In this study,\nacid-sensitive release methacrylated hyaluronic acid (HAMA) microspheres\nwere constructed by using microfluidic technology, which can be used\nas a targeted drug delivery system for intervertebral disc degeneration\n(IVDD) through Schiff base chemical bonding on the surface of the\nmicrospheres to achieve intelligent drug release. Interleukin-1 receptor\nantagonist (IL-1 Ra) is a naturally occurring anti-inflammatory antagonist\nof the interleukin-1 family of pro-inflammatory cytokines. Despite\nits outstanding broad-spectrum anti-inflammatory effects, IL-1 Ra\nhas a short biological half-life (4–6 h). The slow-release\nperformance of IL-1 Ra can be greatly improved using bovine serum\nalbumin nanoparticles (BNP). In addition, the modified HAMA microspheres\nexhibited good injectability and porosity, and efficient and uniform\nloading of nanoparticles was achieved via the Schiff base bond. The\ninflammatory microenvironment can be significantly reversed by transporting\nthe modified HAMA microspheres-BNPs (Modified MS) to the degenerative\nnucleus pulposus.