The primary mechanism that causes cartilage damage in osteoarthritis is the progressive change within the cartilage, characterized by the breakdown of extracellular matrix (ECM), chondrocyte apoptosis, inflammation or catabolism, and oxidative stress. Chondrocyte hypertrophy is characterized by increases in size and volume, the expression of collagen type X (COL-X) and matrix metalloproteinase 13 (MMP13), and the marking of terminal differentiation of these cells. In the present chapter, we would like to highlight the role of some specific cytokines, namely transforming growth factor-𝜷3 and interleukin-1 receptor antagonists’ bioconjugation to silk matrices towards the regeneration of articular cartilage. In primary chondrocytes and mesenchymal progenitor cells, silk fibroin has already been demonstrated to activate the Wnt pathway intrinsically. The SF-G bioink shows the ability to reduce hypertrophy during chondrogenesis. Bioconjugation of cytokines with silk matrices will thus play a crucial role in cartilage regeneration.