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Biomimetic process design for tissue regeneration:
from bench to bedside via in silico modelling

Final Report Summary - BRIDGE (Biomimetic process design for tissue regeneration: from bench to bedside via in silico modelling)

Tissue engineering (TE), the interdisciplinary field combining biomedical and engineering sciences in the search for replacements of diseased/non-functional organ (parts) by manufactured living implants that support functional tissue regeneration, has key issues with the quantity and quality of the generated products. Protocols and procedures followed in the lab are mainly trial and error based, requiring a huge amount of manual interventions and without clear early time-point quality criteria to guide the process. Consequently, these processes are very hard to scale up to industrial production levels. The BRIDGE project has contributed to the fortification of the engineering aspects of the TE field by adding a higher level of understanding and control to the production process through the use of in silico models. BRIDGE has reached the following results:
1. proof-of-concept of the use of an in silico blue-print for the design and control of cell culture for osteo-chondral applications;
2. proof-of-concept of the use of in silico models calculating the niches forming inside 3D bioreactor environments during culture for model-based control of the TE manufacturing processes;
3. model-derived optimised culture conditions increasing quantity and quality of the in vivo outcome of the TE manufacturing process.
4. in silico identification of a limited set of in vitro biomarkers that is predictive of the in vivo outcome;
5. incorporation of congenital defects (neurofibromatosis type I) in the in silico models of osteochondral regeneration allowing for in silico clinical trials for the orphan disease, a necessary step towards the realization of in silico (regenerative) medicine.
The BRIDGE project has successfully integrated research activities in both tissue engineering and mathematical modelling of biological processes, and has taken/is taking important steps toward a rationalized, engineering approach to design and control bone TE manufacturing processes.