Toward better drug development: Three-dimensional bioprinting in toxicological research

Abstract

The importance of three-dimensional (3D) models in pharmacological tests and personalized therapies is significant. These models allow us to gain insight into the cell response during drug absorption, distribution, metabolism, and elimination in an organ-like system and are suitable for toxicological testing. In personalized and regenerative medicine, the precise characterization of artificial tissues or drug metabolism processes is more than crucial to gain the safest and the most effective treatment for the patients. Using these 3D cell cultures derived directly from patient, such as spheroids, organoids, and bioprinted structures, allows for testing drugs before administration to the patient. These methods allow us to select the most appropriate drug for the patient. Moreover, they provide chance for better recovery of patients, since time is not wasted during therapy switching. These models could be used in applied and basic research as well, because their response to treatments is quite similar to that of the native tissue. Furthermore, they may replace animal models in the future because these methods are cheaper and can avoid interspecies differences. This review puts a spotlight on this dynamically evolving area and its application in toxicological testing.

Keywords: ADME test; Drug development; Liver; Organoid; Spheroid; Three-dimensional printing.

Figure 1

The main steps of the drug development process. Image created with BioRender.com.

Figure 2

Structure and cell types of the liver. (A) The hexagonal building blocks determine the metabolic activity of the cells. (B) Cells that play key roles in drug metabolism, niche and homeostasis of the liver. Image created with BioRender.com.

Figure 3

The micropatterned co-cultures. In these co-cultures, the hepatocytes placed in individual islets on a plate, and then fibroblasts or endothelial cells were seeded around them. Image created with BioRender.com.

Figure 4

Drug discovery and personalized medicine using organoids. Created with BioRender.com.

Figure 5

3D models in toxicology testing. Created with BioRender. com. 3D cell cultures can be developed for drug testing so as to allow the selection of suitable medicine for patients.

Figure 6

The main types of 3D bioprinting. Despite the fact that different technological solutions are used, the basis and principle of printing are similar in each case. Image created with BioRender.com.