CARTiPLEX: Advanced Manufacturing and 3D Bioprinting of Complex Stratified Cartilage Tissues

Current tissue engineering strategies based on combinations of stem cells, growth factors and biomaterials, rely on trial and error approaches, giving limited and unpredictable in vivo outcomes. Recently a biomimetic methodology for in vitro process design was described, inspired by in vivo developmental stages of tissue formation. This strategy suggests a gradual and concerted progression of cell growth and differentiation, leading to the organization of cells into tissue structures. As a paradigm, growth plate development will be used to pursue the manufacturing of complex stratified cartilage tissues, ex vivo. A modular bottom-up strategy, based on the use of advanced bioreactor systems and 3D printing, will allow controlled stem cell aggregation, growth, differentiation and the assembly into macrotissue structures. These cartilage tissues will be explored for their biological potential in animal models of large bone defect healing and the repair of deep joint surface defects. The technologies developed in terms of novel bioreactor systems and innovative end-products (3D printed tissues) contributes broadly to the field of scaffold-free tissue manufacturing for tissue engineering and regenerative medicine.