Remotely Controlled 3D-Engineered Scaffolds for Biomimetic In Vitro Investigations on Brain Cell Cocultures

Most in vitro studies regarding new anticancer treatments are performed on 2D cultures, despite this approach imposes several limitations in recapitulating the real tumor behavior and in predicting the effects of therapy on both cancer and healthy tissues. Herein, advanced in vitro models based on scaffolds that support the 3D growth of glioma cells, further allowing the cocultures with healthy brain cells, are presented. These scaffolds, doped with superparamagnetic iron oxide nanoparticles and obtained through 2-photon polymerization, can be remotely manipulated thanks to an external magnet, thus obtaining biomimetic 3D organization recapitulating the brain cancer microenvironment. From a geometric point of view, the structure is functional to both cell culture on individual unit scaffolds and to tailored cocultures fostered by magnetic-driven unit assembly, also allowing for cell migration thanks to passages/fenestrations on adjacent structures. Leveraging magnetic dragging, for which a mathematical model is introduced, multiple cocultures are achieved, highlighting the high versatility and the user-friendly character of the proposed platform that can help overcome the current challenges in 3D cocultures handling, and open the way to the construction of increasingly biomimetic artificial systems.