Nano-elemental selenium particle developed via supramolecular self-assembly of chondroitin sulfate A and Na₂SeO₃ to repair cartilage lesions

Cartilage repair is a significant clinical issue due to its restricted ability to regenerate and self-heal after cartilage lesions or degenerative disease. Herein, a nano-elemental selenium particle (chondroitin sulfate A‑selenium nanoparticle, CSA-SeNP) is developed by the supramolecular self-assembly of Na₂SeO₃ and negatively charged chondroitin sulfate A (CSA) via electrostatic interactions or hydrogen bonds followed by in-situ reducing of L-ascorbic acid for cartilage lesions repair. The constructed micelle exhibits a hydrodynamic particle size of 171.50 ± 2.40 nm and an exceptionally high selenium loading capacity (9.05 ± 0.03 %) and can promote chondrocyte proliferation, increase cartilage thickness, and improve the ultrastructure of chondrocytes and organelles. It mainly enhances the sulfation modification of chondroitin sulfate by up-regulating the expression of chondroitin sulfate 4-O sulfotransferase-1, −2, −3, which in turn promotes the expression of aggrecan to repair articular and epiphyseal-plate cartilage lesions. The micelles combine the bio-activity of CSA with selenium nanoparticles (SeNPs), which are less toxic than Na₂SeO₃, and low doses of CSA-SeNP are even superior to inorganic selenium in repairing cartilage lesions in rats. Thus, the developed CSA-SeNP is anticipated to be a promising selenium supplementation preparation in clinical application to address the difficulty of healing cartilage lesions with outstanding repair effects.