From plant to prosthesis: An engineered biomimetic disc repairs senescence-associated intervertebral disc degeneration in goats.

Abstract

Intervertebral disc degeneration (IVDD) is a multifactorial process driven by oxidative stress, inflammation, and cellular senescence, ultimately leading to disc destruction and functional loss. Current treatments can only alleviate symptoms such as low back pain to a certain extent, without addressing the underlying imbalance in the disc microenvironment. In this study, we successfully developed an engineered biomimetic disc, IHP@Yam, which synergistically combines the mesoporous Prussian Blue (HMPB) as a nanozyme and isoliquiritigenin (ISL) for reactive oxygen species (ROS) scavenging, anti-inflammatory, and anti-aging effects, and uses a high-adhesion, highly elastic nature-based yam-derived hydrogel as a disc, aimed at remodeling the degenerative intervertebral disc microenvironment. In vitro experiments demonstrated that isoliquiritigenin-loaded hollow mesoporous prussian blue (IHP) significantly reduced the expression of inflammatory cytokines (TNF-α, IL-1β), matrix-degrading enzymes (MMP9, MMP13), and senescence markers (P16, P21), while promoting the expression of anabolic matrix proteins (ACAN, COL-II), and reducing apoptosis and the number of SA-β-gal-positive cells. Transcriptomic sequencing indicated that IHP treatment markedly inhibited the NF-κB signaling pathway while promoting activation of the AMPK pathway. This was further validated by the downregulation of genes associated with pro-inflammatory signaling, supporting the protective effects observed following IHP intervention. In vivo studies using rat and goat IVDD models showed significant retention of nucleus pulposus hydration, while histological staining confirmed abundant deposition of ACAN and COL-II. In the high-intensity mechanical stress environment of large animal models, IHP@Yam effectively preserved the disc height index (DHI) and inhibited the expression of matrix-degrading enzymes. This study confirms the excellent performance of the IHP@Yam biomimetic disc in improving the degenerative disc microenvironment, providing a reliable therapeutic strategy for intervertebral disc degeneration.