Poster Presentation: Byungjun Kang

ABSTRACT

An integrated in vivo–ex vivo platform for mechanobiological regulation of metastasis

Byungjun Kang1, Kathryn Regan1, Gabrielle Grifno1, Lauren Castle1, Linzheng Shi1, Anissa Benzaid-Williams2, William Boley2,3, and Hadi T. Nia1.

1Department of Biomedical Engineering, Boston University
2Department of Mechanical Engineering, Boston University
3Department of Materials Science, Boston University

Objective: The lung is a frequent site of metastasis. While breathing applies mechanical forces to cells in the lung, how these forces influence metastasis remains unclear. In vitro systems lack native lung physiology while in vivo models cannot selectively regulate lung mechanics at the lobe level. In this study, we developed in vivo and ex vivo models, with complementary features, that enable lobar regulation of breathing mechanics to study mechanobiological regulation of metastasis (Figure 1A and 1B).

Methods: For in vivo model we fabricated an air-restriction plug using a high-resolution 3D printer (BMF S240) and coated it with polyacrylamide hydrogel. The plug with the internal air flow channel was then introduced into the bronchus of a specific lobe of a mouse lung (Figure 1A, 1C, and 1D). The plug will result in differential ventilation of the lobes during spontaneous breathing. For ex vivo model, the plugs inserted into the bronchi in the left and right lobes of the lung in the ex vivo crystal ribcage were connected to separate ventilators (Figure 1B). Lung tissue structure was visualized using X1 confocal microscope (Nikon) following Evans blue labeling. Green fluorescent protein (GFP)-expressing tumor cells were injected into a C57BL/6 wild-type mouse through the tail vein.

Results and conclusion: When the plug with a small air channel was inserted, the alveoli in the lobe with the plug did not exhibit pressure-induced expansion unlike those in the lobe without the plug (Figure 1E). The ex vivo model could selectively control the motion of each lobe (Figure 1F). The number of cancer cells trapped in the lobe under higher tidal volume was greater than those in the lobe with lower tidal volume (Figure 1G and 1H). These systems will be used to investigate how mechanical forces regulate later metastatic processes.