Abstract

Articular cartilage injury often leads to vascular endothelial cell (VEC) infiltration, disrupting the microenvironment between cartilage and subchondral bone, thereby compromising cartilage repair quality. Curcumin (Cur) is a natural polyphenol with anti-inflammatory and anti-angiogenic properties that holds promise for therapeutic applications. However, its clinical utility is limited due to poor solubility and instability. To address these challenges, we developed a curcumin-loaded silk fibroin nanoparticle (Cur-SN) delivery system to inhibit VEC infiltration and promote cartilage regeneration. Cur-SNs were prepared and characterised to evaluate their physicochemical properties. The effects of Cur-SN on VEC apoptosis and senescence were assessed, and the underlying mechanism by which Cur-SN regulates mitochondrial homeostasis via the Drp1/ROS pathway was investigated. Additionally, a rat knee cartilage defect model was established, in which Cur-SN combined with a BMSC-loaded hydrogel was implanted. Cartilage differentiation and VEC infiltration levels in newly formed tissues were subsequently analysed. In vitro experiments demonstrated that Cur-SN upregulated Drp1 and ROS levels, leading to mitochondrial homeostasis disruption. This, in turn, induced VEC apoptosis and senescence while significantly inhibited VEC infiltration. Furthermore, Cur-SN effectively counteracted the inhibitory effects of VEC activation on BMSC chondrogenic differentiation. In vivo experiments revealed that Cur-SN reduced VEC infiltration and angiogenesis in newly formed tissues, thereby promoting hyaline cartilage regeneration at the defect site. Cur-SN enhances cartilage repair by upregulating Drp1 expression and ROS levels, thereby disrupting mitochondrial homeostasis, inducing VEC apoptosis and senescence, and inhibiting VEC infiltration.