Plug-and-Play Lymph Node-on-Chip: Possibility of Passage of Polymer Capsules to Secondary Tumor, Designed By Combination Of Cell Spheroid, Collagen Sponge and T-cells

Towards the improvement of the efficient study of drugs and contrast agents, the 3D microfluidic platforms are currently being actively developed for testing these substances and particles in vitro. Such bioengineering solutions, can bring the system much closer to real-world conditions without the unnecessary use of laboratory animals. Also, the application of engineering methods allows the fine-tuning of the resulting structures for their installation and long-term observation in imaging systems. We have elaborated a microfluidic lymph node-on-chip (LNOC) as a tissue engineered model of a secondary tumor in lymph node (LN) formed due to the metastasis process. The developed chip has a collagen sponge with a 3D spheroid of 4T1 cells located inside, simulating secondary tumor in the lymphoid tissue. This collagen sponge has a morphology and porosity comparable to that of a native human LN. To demonstrate the suitability of the obtained chip for pharmacological appli-cations, we used it to evaluate the effect of contrast agent/drug carrier size, on the penetration and accumulation of particles in 3D spheroids modeling secondary tumor. For this, the 0.3, 0.5 and 4 μm bovine serum albumin (BSA)/tannic acid (TA) capsules were mixed with lymphocytes and pumped through the developed chip.
Thus, in our study, 0.3 μm capsules, which penetrated well into the spheroid, turned out to be the most effective for delivery. These results highlight the potential of our LNOC for use in particle and contrast agent testing. They also demonstrate that the LNOC is an attractive alternative for further analysis and understanding of the effectiveness of developed drug delivery vehicles and contrast agents delivered to cells and organs. Moreover, some findings that we have obtained during the development of our device can be used for the elab-oration of other types of lab-on-chip systems.