Research database

Biofabrication is an emerging field that identifies the set of processes required for the “automated generation of biologically functional products with a structural organization through bioprinting or bioassembly and subsequent tissue maturation processes”. Biofabrication technologies have the potential to revolutionize the Regenerative Medicine and Organs-on-Chip (OoC) domains. This project innovates in the domain of computational tools to support 2D/3D biofabrication technologies. Its goal is the “development of a software framework, from now on called Saisei Protocol Generator (SPG), capable of generating optimal protocols to improve the biofabrication of complex in vitro models using static and dynamic 2D/3D co-culture techniques”. The SPG framework combines two crucial elements designed during the project. First, a multi-scale modeling strategy allows modeling and simulating an entire co-culture system, including the automated culture environment and the target biosystem. Second, a multi-objective Design Space Exploration engine exploits simulations to generate optimized biofabrication protocols. The project has the potential to significantly improve the efficiency of the development of a new biofabrication protocol by exploiting massive low-cost in silico simulations rather than more expensive in vitro experiments. The project aims at validating its results in the domain of the biofabrication of 2D and 3D in vitro co-cultures of human mesenchymal and endothelial cells intended to mimic the natural bone regeneration process for both pharmacological tests and regenerative purposes. Co-cultures will be performed under static and dynamic conditions using insert-based two-chamber co-cultures (for paracrine only cross-talk) and spheroid co-cultures (for paracrine and physical cross-talk in the same matrix support). Both applications require correctly recapitulating the phenotypic features linked to the paracrine cross-talk between mesenchymal and endothelial cells in terms of cell differentiation, metabolism, proliferation, and morphogenesis, underlying neo-vascularization potential in bone regeneration. The latter event is particularly relevant since angiogenesis and vascular endothelial remodeling sustain the metabolic demand of bone growth. The proposed research plan and the multidisciplinary synergy among Computational Biology, Bioengineering, and Cell Biology available in this project move a step forward toward the concept of intelligent and digitized biofabrication.