Computationeel kader voor de biologische optimalisatie weefselengineering constructen.

Biomanufacturing offers great potential for tissue engineering (TE) as it allows the creation of living constructs with controlled, spatial organizations (patterns) of living cells, instructive signals and carrier materials. Patterned constructs are hypothesized to enhance bone regeneration, compared to uniform constructs because their organization can be tailored to the host environment of the defect. However, optimizing the construct design is far from trivial due to the combinatorial explosion of design degrees of freedom as well as the non-intuitive spatiotemporal dynamics of the bone regeneration process. Multiscale computational modeling can address this challenge by quantitatively investigating the relation between the spatial pattern of cells and signals and the resulting bone healing outcome. Although many approaches in the literature exist for the optimization of structural parameters of porous scaffolds, computational frameworks for the biologically informed optimization of patterned constructs in relation to the host environment are non-existing. This project will establish such a framework, by refining a bioregulatory model of bone regeneration with an accurate description of the interaction between the host environment and the implanted TE construct. Moreover, a thorough calibration and validation to in vivo data will be performed. Finally, this multiscale computational framework will be used to optimize the biological design parameters of patterned constructs