A methodology for co-simulation-based optimization of biofabrication protocols

Biofabrication processes are complex and often unsatisfactory. Trial-and-error methods are costly and yield only incremental innovation, starting from sub-optimal and poorly represented existing processes. Although computational techniques might support efficient process design to find optimal process configurations, intelligent computational approaches must comprise biological complexity to provide meaningful insights. This paper proposes a novel co-simulation-based optimization methodology for the systematic design of protocols for cell culture and biofabrication. The proposed strategy integrates evolutionary computation and simulation for efficient design space exploration and assessment of candidate protocols. A generic library supports the modular and flexible composition of multiscale and multidomain co-simulation scenarios. The feasibility of the presented approach was demonstrated in the automatic generation of protocols for the biofabrication of an epithelial cell monolayer. The results are twofold. First, the prototype co-simulation library helps build flexible, loosely coupled simulation scenarios. Second, the in-silico experimentation on the use case shows that the proposed approach is a viable first step towards standard and automated design in biofabrication.