Medical research is only as good as the model, whether you’re using one animal to stand in for another, or creating in vitro replicas of tissue and organs. A research lab at Drexel University specializing in biofabrication recently used 3D printing to create models of tumor tissue that more closely replicate real tumors than traditional 2D tissue culture. Appropriating tools in this manner could lead to a better understanding of how tumors grow, and importantly, how they die.
It’s already known that tumors in the body vary from lab-grown tissue in their amount of surface area, the shape of the cells, and cellular composition. When potential cancer drugs are screened on these lab-grown cultures, the artificial cells are less resistant to drugs, leading to false hopes and inaccurate information.
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Dr. Wei Sun’s research first analyzed the best techniques for deposition printing both Hela cells (a famous strain known as the responsible party for cervical cancer) and a support matrix similar to the proteins that would be found surrounding tumor cells in an organism. Then the team compared how chemoresistant the resulting tumor was relative to a 2D tissue culture of the same cells.
The conditions required for 3D printing, primarily heat and mechanical force, are both detrimental to living cells, so a hearty line of cells was chosen for the initial test until the process could be fine-tuned for future cell lines.
However, heat is also required for a proper viscosity of the fibrin, alginate, and gelatin combination that is used to mimic the support proteins in which cells naturally grow. Too hot, and the cancer cells die; too cold and too much force is required to extrude the gelatinous mixture, and the cells die. Addressing these issues allowed the researchers to turn their attention to the process of printing.
Printing cells allows researchers to mimic natural growth patterns. Channels in the printed structure facilitate the transport of oxygen, nutrients, and waste, similar to natural tissues. After eight days of growth, 90 percent of the cells were still alive and the tissue had organized into a spheroid of cells, with tight cell-cell connections, where 2D cultures contain cells that are flat and elongated. The 3D-printed cells also proliferated at a higher rate, similar to how tumor cells naturally grow.
Fluorescently marked tumor spheroids eight days after being printed, where blue represents the cell and the green the extracellular materials
After proving the process would work to create viable and living tissue, the next step was even more important: evaluating if it was a more authentic model for testing cancer drugs. In tests with paclitaxel, the tumor spheroids were more chemically resistant than the 2D tissues, consistent with expectations from naturally-occurring tumors.
Future plans for research include printing with multiple types of cells, similar to tumors removed from humans, and embedding printed cells onto other printed tissues to further simulate how tumors really grow.
In 2002 Sun created a 3D printer so his biofabrication lab could create tissue samples and bone scaffolds. Recently we’ve seen researchers print a skull as well as a replacement ear out of cartilage cells.
The research was originally published in Biofabrication. In the video below, you can watch Sun’s multi-nozzle printer demonstrating the deposition of multiple biological substances.
Source: Drexel University