Despite significant achievements in the field of regenerative medicine and the enormous potential for engineered tissue products, significant hurdles have prevented cellular therapies from gaining wide-spread clinical adoption. Manufacturing related issues have been proposed as key challenges to be addressed for the translation of regenerative therapies to the clinic and the successful commercialization of engineered products. Similar to other biotechnology sectors (e.g., vaccines or recombinant protein production), bioreactor systems could play a central role in establishing engineered tissues in the clinic. In fact, by automating and streamlining manufacturing processes, they would allow to improve product reproducibility, safety, standardization and possibly reach cost-effectiveness. This project aims at the development, pre-clinical and clinical testing of a sensor-based bioreactor system for the production of functional, autologous engineered grafts with reproducible properties. The bioreactor-based manufacturing paradigm will be addressed in the specific context of cartilage repair. Innovative features of the proposed tissue engineering strategy will include: (i) an automated and controlled production system, (ii) bioreactor conforming to regulatory guidelines, (iii) simplified, streamlined, and scalable tissue engineering process, (iv) on-line monitoring of culture/quality parameters, and (v) data management systems for traceability. To achieve these goals, BIO-COMET brings together internationally renowned leaders in the field of regenerative medicine, from academic, clinical and industrial research institutions. Successful implementation of the project will be instrumental to extend use of bioreactor-based platforms beyond cartilage tissue engineering, with the ultimate goal to facilitate broad utilization and commercialization of cell-based grafts as therapeutic solutions.