Published April 18, 2022
Bioprinting, especially 3D printing, is opening doorways to in vitro drug discovery and toxicology research. Increasing the utility of in vitro studies, 3D printing can help replace animal studies and avoid errors in translating the results across to human physiology.
Tools like the Corning Matribot® Bioprinter expand research horizons and bring consistency through automation to high-throughput approaches such as organoid and spheroid culture. In addition, being able to use the patient's own cells in printing can also make it easier to obtain meaningful therapeutic results in personalized medicine.
3D Tissue as In Vitro Mimics
3D bioprinting can involve creating layer-by-layer models that mimic tissues and organs. This is done by seeding living cells within a supportive extracellular matrix ink (bioink) and then printing up a tissue replica.
By using software and precision printing tools researchers can layer or print cells in a close approximation to the ways cells orient within natural tissues. The result is an organ or tissue model that better represents the in vivo environment. This is important for studying cell-cell interactions that are essential to tissue and organ function.
Sacrificial inks are also available to create scaffolding for vascularized 3D bioprints that mimic organ structure even more closely.
Software Tools Print for Cellular Orientation
As Corning Applications Scientist Hilary Sherman notes, "With 3D printing, you can actually direct the three-dimensional structure. You can form layers of tissues where the cells are in a specific location or specific orientation, rather than randomly growing in culture." Bioprinters such as the Matribot bioprinter often come complete with CAD files, which are easy to use in setting up a new tissue print. More are available online, making 3D printing an incredibly accessible and versatile investment.
Sherman goes on to give the example of skin, which is made up of fibroblasts topped by keratinocytes. "Those are different, distinct cell types, and their orientation matters if we want to create a good model," she says.
Instead of in vitro cultures composed entirely of a single cell type, such as fibroblasts, toxicology research and cosmetic screening can be carried out on layered prints that mimic skin anatomy.
"Simply having a co-culture in a dish is really not enough," says Sherman. "We want to create a structure in which the cells are organized in a way that's more similar to how they're organized in the body in order to see the true impact."
"At the most basic research level, 3D bioprinting gives a better understanding of how multiple cell subtypes interact together," explains Sherman. "In the example of skin, if you want to study the impact of a lotion or something that gets placed on top of the skin, it wouldn't make sense to test your compound with fibroblasts, because that's not what's actually exposed to the drug. It makes more sense to expose it to the keratinocytes which are on the top layer, but with them interacting with the fibroblasts."
Extrusion Versatility for Organoid Consistency
Being able to accurately dispense bioinks helps with consistency. The Corning Matribot bioprinter, for example, is the only benchtop 3D printer that can dispense a cell matrix product, Corning Matrigel® matrix, with accuracy, as its extrusion tip is temperature controlled.
Not only does this help with cell orientation and precision within the bioprint, but it also means that accurately dispensing cells or organoids in temperature sensitive hydrogels is possible. This is important for toxicology research since data from studies will be highly consistent.
Frontiers in Medical Technology notes that creating heterogeneous tissues for drug screening in personalized medicine studies is highly important for validity. Being able to recreate 3D bioprints accurately helps to bridge between in vitro and in vivo by providing study materials that have biological relevance to living tissue.
The temperature-controlled tip is key. "Doing it by hand is really challenging," explains Sherman, "because instead of having a temperature-controlled head that holds your syringe, you need to pre-chill all your pipette tips and then use ice baths and work very quickly. It's just more challenging."
Automation and Scaling Up for High Throughput
Drug discovery and toxicology studies rely on scale and repeatability for meaningful data. The ability to automate dispensing can lead to consistent designs suitable for high-throughput applications, such as multiwell plate assays and automated plate readers. Choosing a 3D bioprinter such as the Matribot bioprinter, which can dispense temperature-sensitive viscous solutions with high levels of accuracy into a multitude of vessels, supports scaling up.
Personalized Medicine: Bioprinting for Hard-to-Source Cells
Drug discovery studies often rely on using hard-to-source cells, such as those obtained from a particular patient's cancer biopsy. Archives in Toxicology notes that 3D bioprinting techniques are often ideal for screening chemotherapy drugs to identify the best option.
Sherman describes how this approach helps patients with cystic fibrosis:
"The most notable cell type for most organoid researchers would be cystic fibrosis because those were the first ever organoids used to treat a patient," she explains. "Since cystic fibrosis can be caused from a variety of different mutations and not any one in particular, it's really hard to treat because everybody's needs are different. Patient biopsies have been screened to determine what is the best drug or combination of drugs to treat a specific individual's cystic fibrosis."
