Enhancing Tissue Formation via Artificial-Natural Cell Communication: Osteogenic Differentiation of C2C12 Myoblasts in a 3D Bioprinted Scaffold

The recent increase in tissue and organ-related health problems and the limitations associated with conventional clinical treatments have pointed out the importance of discovering new strategies to improve the wellness of patients. From this perspective, tissue engineering has proven to be a promising approach since it can replicate natural tissues' structural and physiological properties via well-established communication pathways between living cells and biomacromolecular cues. In parallel, the bottom-up reconstruction of living systems has gained interest, mainly focusing on the development of artificial cells, synthetic engineered platforms that aim to replicate natural cell behavior in vitro. These single building blocks can contribute to create a complex communication network between living and artificial cells via the exchange of signaling molecules to activate specific differentiation pathways. Furthermore, the combination of tissue engineering applications, such as 3D bioprinting, with artificial cell studies can help engineering hybrid structures, where the researchers can achieve spatiotemporal control over cell behavior. In accordance with this, we propose an artificial-cells system-mediated differentiation that exploits 3D bioprinting to obtain a well-defined three-dimensional structure for bone tissue regeneration purposes. In this context, bone morphogenic protein-2 loaded peptide-based coacervates were designed and incorporated into the bioink in combination with C2C12 myoblasts. The cell-laden hydrogel was then 3D bioprinted, and the transdifferentiation pathway of C2C12 myoblasts into osteoblasts was exploited by establishing a controlled uptake/release mechanism within the artificial cells