"Tissue engineering (TE), the interdisciplinary field combining biomedical and engineering sciences in the search for functional man-made organ replacements, has key issues with the quantity and quality of the generated products. Protocols followed in the lab are mainly trial and error based, requiring a huge amount of manual interventions and lacking clear early time-point quality criteria to guide the process. As a result, these processes are very hard to scale up to industrial production levels. BRIDGE aims to fortify the engineering aspects of the TE field by adding a higher level of understanding and control to the manufacturing process (MP) through the use of in silico models. BRIDGE will focus on the bone TE field to provide proof of concept for its in silico approach.The combination of the applicant's well-received published and ongoing work on a wide range of modelling tools in the bone field combined with the state-of-the-art experimental techniques present in the TE lab of the additional participant allows envisaging following innovation and impact:1. proof-of-concept of the use of an in silico blue-print for the design and control of a robust modular TE MP;2. model-derived optimised culture conditions for patient derived cell populations increasing modular robustness of in vitro chondrogenesis/endochondral ossification;3. in silico identification of a limited set of in vitro biomarkers that is predictive of the in vivo outcome;4. model-derived optimised culture conditions increasing quantity and quality of the in vivo outcome of the TE MP;5. incorporation of congenital defects in the in silico MP design, constituting a further validation of BRIDGE’s in silico approach and a necessary step towards personalised medical care.We believe that the systematic – and unprecedented – integration of (bone) TE and mathematical modelling, as proposed in BRIDGE, is required to come to a rationalized, engineering approach to design and control bone TE MPs."