Baicalein-loaded porous silk fibroin microspheres modulate the senescence of nucleus pulposus cells through the NF-κB signaling pathway

Abstract

Intervertebral disc degeneration (IVDD), an age-associated degenerative condition, significantly contributes to low back pain, thereby adversely affecting individual health and quality of life, while also imposing a substantial societal burden. Baicalein, a natural flavonoid derived from Scutellaria baicalensis Georgi, demonstrates a range of pharmacological activities, including antioxidant, anti-inflammatory, anti-tumor, and antibacterial properties. This positions it as a promising candidate for the treatment of IVDD through intradiscal drug delivery. However, local degenerative processes and the inherently low fluid exchange within the intervertebral disk are likely to affect drug retention. In this study, we developed baicalein-loaded porous silk fibroin microspheres to extend the drug release profile. Baicalein-loaded porous silk fibroin microspheres were prepared by electrostatic spraying. Subsequent characterization and evaluation of their intrinsic properties were conducted using nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), transmission electron microscopy(TEM), and fourier transform infrared spectroscopy (FTIR). The findings of our study demonstrated that baicalein-loaded porous silk fibroin microspheres exhibited a sustained drug release profile. Consequently, these microspheres effectively inhibited the senescence of nucleus pulposus cells (NPCs), which induced by Tert-butyl hydroperoxide (TBHP). Mechanistic investigation utilizing transcriptome sequencing revealed that the NF-κB signaling pathway is involved in the effects of baicalein-loaded porous silk fibroin microspheres. Furthermore, our findings demonstrated that the microspheres exhibited excellent biocompatibility in rats subcutaneous implantation model. Collectively, we developed a promising biomaterial for the treatment of IVDD, warranting further systematic preclinical investigation.