The modeling of pathological microenvironments of the central nervous system (CNS) represents a disrupting approach for drug screening for advanced therapies against tumors and neuronal disorders. The in vitro investigations of the crossing and diffusion of drugs through the blood-brain barrier (BBB) are still not completely reliable, due to technological limits in the replication of 3D microstructures that can faithfully mimic the in vivo scenario. An innovative 1:1 scale 3D‐printed realistic biohybrid model of the brain tumor microenvironment, with both luminal and parenchyma compartments, has been developed. The dynamically-controllable microfluidic device, fabricated through two‐photon lithography, enables the triple co‐culture of hCMEC/D3 cells, forming the internal endothelium of the capillaries, of astrocytes, and of magnetically‐driven spheroids of U87 glioblastoma cells. Tumor spheroids are obtained from culturing glioblastoma cells inside 3D microcages loaded with superparamagnetic iron oxide nanoparticles. The system demonstrated to be capable in hindering dextran diffusion through the bioinspired BBB, while allowing chemotherapy‐loaded nanocarriers to cross it.
The proposed biomimetic dynamic 3D system represents a drastic innovation with respect to other models well established in the literature and available on the market, since it will allow to reliably reproduce the physio-pathological environment and to accurately estimate the amount of drugs and/or of nanomaterial-associated compounds delivered through a modular length of the system. The proposed platform can be easily adopted in cell biology laboratories as multi-compartmental scaffold for the development of advanced co-culture systems, the primary biomedical applications of which consist in high-throughput screening of brain drugs and in testing of the efficacy of different anticancer therapies in vitro.
