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The repair of cartilage and bone tissue post arthritis or injury in the knee joint is a challenge to the orthopedics. Both doxycycline and collagen scaffolds had been shown with positive influences on the repair of the tissue. Doxycycline inhibits catabolism related enzymes. Collagens provide tissue repair materials. In this study, the influence of doxycycline and jellyfish collagen (JFC) scaffold to the cells in vitro and tissue repair in vivo was studied. Doxycycline was found with a broad inhibition of the matrix metallopeptidases. It also had an enhancement to the progenitor chondrocytes but suppressed the maturation of chondrocytes. JFC (major type II collagen) was seen had improved both type I and type II collagen production during chondrogenesis of mesenchymal stem cells in vitro. Both doxycycline and JFC enhanced the bone formation and had synergistic effects in a late-stage during the bone repair process. However, the cartilage repair was found with no significant influence after the implantations. Overall, the control of metabolism by doxycycline and providing stimulation to collagen production by the implantation of JFC only contribute to bone growth but had little influence on cartilage repair. This indicates the growth of cartilage tissue needs more delicate regulation. The subchondral bone repair, even with some chondrocytes and proteoglycan deposition in the extracellular matrix could not convert to a repair with mature hyaluronic cartilage tissue.