Factors Modulating Chondrogenesis and Mechano-Inductive Systems for Cartilage Tissue Engineering from Mesenchymal Stem Cells: A Review

Cartilages have a very little capability for self-repair after injury. Tissue engineered bio-scaffolds seeded with the mesenchymal stem cell (MSC)-derived chondrocytes are viewed as a promising therapeutic modality for regeneration enhancement of the damaged cartilages. Under appropriate culture conditions, MSCs can differentiate into chondrocytes and secrete collagen (Col2a1 (IIb)), proteoglycans (aggrecan (Agc)), non-collagenous proteins, and tissue fluid to lead to the development of zones of organization in cartilages. Bioreactor can provide the mechanical and chemical stimuli along with the required cytokines (Cytl1, TNF-α, ROS), mitogen (IL-18, FGF-2, Protein Kinase C-Erk-1/2 and p38), and growth factors (IGF-1, TGF-β, parathyroid hormone-related peptide, BMP-2) to modulate chondrogenesis and grow threedimensional (3-D) tissue. It also allows changes in the culture environment to affect the kinetics and properties of tissue growth, in a well-defined fluid regime to elucidate mechanotransduction pathways involving shear, perfusion, and compression force and tissue growth kinetics. This review discusses various signalling factors in the regulation of chondrogenesis from MSCs and elaborates various types of bioreactors that may provide optimal culture milieu and mechanical stress which are used to develop the tissue-engineered cartilages for their clinical application.