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.

High-throughput fabrication of cell spheroids with 3D acoustic assembly devices

“…The IC 50 value was further calculated. Figure 6b shows that the IC50 value of spheroids (16.03 μM) was slightly higher than 2D cultures (13.52 μM), indicating higher drug resistance in spheroids, which could be attributed to several characteristics of 3D cultures [ 4 - 7 ] . In addition, the dead cell percentage increased rapidly in both 2D and spheroid cultures as the 268 concentration of sorafenib increased, showing a dosedependent response to the drug.…”

“… 261 During the last decades, cell spheroids as advantageous models were used in various biomedicine studies, such as drug screening [ 1 ] , disease modeling [ 2 ] , tissue engineering, and regenerative medicine [ 3 ] . Compared to commonly two-dimensional (2D) monolayer cultures, tumor spheroids represent better in vivo histological and biological characteristics, such as three-dimensional (3D) distribution of nutrients, metabolites and oxygen, as well as complex interactions of cells and extracellular matrix [ 4 ] , making their drug responses similar to those found in vivo [ 5 - 7 ] . More recently, cell spheroids as building blocks promise to bring tissue engineering to next level [ 8 - 10 ] .…”

High-throughput fabrication of cell spheroids with 3D acoustic assembly devices

“…The IC 50 value was further calculated. Figure 6b shows that the IC50 value of spheroids (16.03 μM) was slightly higher than 2D cultures (13.52 μM), indicating higher drug resistance in spheroids, which could be attributed to several characteristics of 3D cultures [ 4 - 7 ] . In addition, the dead cell percentage increased rapidly in both 2D and spheroid cultures as the 268 concentration of sorafenib increased, showing a dosedependent response to the drug.…”

“… 261 During the last decades, cell spheroids as advantageous models were used in various biomedicine studies, such as drug screening [ 1 ] , disease modeling [ 2 ] , tissue engineering, and regenerative medicine [ 3 ] . Compared to commonly two-dimensional (2D) monolayer cultures, tumor spheroids represent better in vivo histological and biological characteristics, such as three-dimensional (3D) distribution of nutrients, metabolites and oxygen, as well as complex interactions of cells and extracellular matrix [ 4 ] , making their drug responses similar to those found in vivo [ 5 - 7 ] . More recently, cell spheroids as building blocks promise to bring tissue engineering to next level [ 8 - 10 ] .…”

Understanding the Toxicity of Metal-Based Nanomaterials: Current Insights, Challenges, and Future Directions

“…218 Tissue bioprinting also holds promise when relating to biological assessments of nanomaterials, as this technology consists of computational mapping and subsequent buildup of matrices containing cells and bioinks that, under proper culture conditions, can mimic organ tissue (to a certain extent); therefore, allowing work on a model closer to reality for toxicological screening. 219 Another disruptive technology is microfluidics systems, also known as organ-on-a-chip (OCC). These microphysiological systems consist of designed channels that can integrate cells (even 3D models) and physiological and physicochemical microenvironments that allow for the reconstruction of tissue microarchitecture and function, incorporating matrices and flux of bioactive molecules and/or others that can mimic the static biological environment and its dynamic flux.…”

Functional Liver Cell–Based Platforms in Biomedical Research

“…3D cultures are valuable, especially in precision research such as individual drug response studies and evaluation of long‐term effects of drugs. This approach enhances the predictive accuracy of in vitro drug toxicology assays and is suggested as the preferred method in many drug screening studies [ 77 ].…”

High-throughput fabrication of cell spheroids with 3D acoustic assembly devices

“…The IC 50 value was further calculated. Figure 6b shows that the IC50 value of spheroids (16.03 μM) was slightly higher than 2D cultures (13.52 μM), indicating higher drug resistance in spheroids, which could be attributed to several characteristics of 3D cultures [ 4 - 7 ] . In addition, the dead cell percentage increased rapidly in both 2D and spheroid cultures as the 268 concentration of sorafenib increased, showing a dosedependent response to the drug.…”

“… 261 During the last decades, cell spheroids as advantageous models were used in various biomedicine studies, such as drug screening [ 1 ] , disease modeling [ 2 ] , tissue engineering, and regenerative medicine [ 3 ] . Compared to commonly two-dimensional (2D) monolayer cultures, tumor spheroids represent better in vivo histological and biological characteristics, such as three-dimensional (3D) distribution of nutrients, metabolites and oxygen, as well as complex interactions of cells and extracellular matrix [ 4 ] , making their drug responses similar to those found in vivo [ 5 - 7 ] . More recently, cell spheroids as building blocks promise to bring tissue engineering to next level [ 8 - 10 ] .…”

Understanding the Toxicity of Metal-Based Nanomaterials: Current Insights, Challenges, and Future Directions

“…218 Tissue bioprinting also holds promise when relating to biological assessments of nanomaterials, as this technology consists of computational mapping and subsequent buildup of matrices containing cells and bioinks that, under proper culture conditions, can mimic organ tissue (to a certain extent); therefore, allowing work on a model closer to reality for toxicological screening. 219 Another disruptive technology is microfluidics systems, also known as organ-on-a-chip (OCC). These microphysiological systems consist of designed channels that can integrate cells (even 3D models) and physiological and physicochemical microenvironments that allow for the reconstruction of tissue microarchitecture and function, incorporating matrices and flux of bioactive molecules and/or others that can mimic the static biological environment and its dynamic flux.…”

Functional Liver Cell–Based Platforms in Biomedical Research

“…3D cultures are valuable, especially in precision research such as individual drug response studies and evaluation of long‐term effects of drugs. This approach enhances the predictive accuracy of in vitro drug toxicology assays and is suggested as the preferred method in many drug screening studies [ 77 ].…”

High-throughput fabrication of cell spheroids with 3D acoustic assembly devices

“…The IC 50 value was further calculated. Figure 6b shows that the IC50 value of spheroids (16.03 μM) was slightly higher than 2D cultures (13.52 μM), indicating higher drug resistance in spheroids, which could be attributed to several characteristics of 3D cultures [ 4 - 7 ] . In addition, the dead cell percentage increased rapidly in both 2D and spheroid cultures as the 268 concentration of sorafenib increased, showing a dosedependent response to the drug.…”

“… 261 During the last decades, cell spheroids as advantageous models were used in various biomedicine studies, such as drug screening [ 1 ] , disease modeling [ 2 ] , tissue engineering, and regenerative medicine [ 3 ] . Compared to commonly two-dimensional (2D) monolayer cultures, tumor spheroids represent better in vivo histological and biological characteristics, such as three-dimensional (3D) distribution of nutrients, metabolites and oxygen, as well as complex interactions of cells and extracellular matrix [ 4 ] , making their drug responses similar to those found in vivo [ 5 - 7 ] . More recently, cell spheroids as building blocks promise to bring tissue engineering to next level [ 8 - 10 ] .…”

Understanding the Toxicity of Metal-Based Nanomaterials: Current Insights, Challenges, and Future Directions

“…218 Tissue bioprinting also holds promise when relating to biological assessments of nanomaterials, as this technology consists of computational mapping and subsequent buildup of matrices containing cells and bioinks that, under proper culture conditions, can mimic organ tissue (to a certain extent); therefore, allowing work on a model closer to reality for toxicological screening. 219 Another disruptive technology is microfluidics systems, also known as organ-on-a-chip (OCC). These microphysiological systems consist of designed channels that can integrate cells (even 3D models) and physiological and physicochemical microenvironments that allow for the reconstruction of tissue microarchitecture and function, incorporating matrices and flux of bioactive molecules and/or others that can mimic the static biological environment and its dynamic flux.…”

Functional Liver Cell–Based Platforms in Biomedical Research

“…3D cultures are valuable, especially in precision research such as individual drug response studies and evaluation of long‐term effects of drugs. This approach enhances the predictive accuracy of in vitro drug toxicology assays and is suggested as the preferred method in many drug screening studies [ 77 ].…”