Combining High-throughput screening and 3D bioprinting1 Comment
The future of drug screening, disease modeling, and precision medicine.
In the last few decades, both high-throughput screening and three-dimensional (3D) bioprinting technologies have emerged and have been proven to be instrumental for the advancement of drug screening, drug development, and tissue modelling.
High-throughput screening (HTS) is well established within the pharmaceutical industry for compound and drug discovery. It is, for the most part, the primary method of testing prior to compound validation and preclinical animal model studies prior to clinical trials. Today, the industry standard is still the use of two-dimensional (2D) cell culture for screening, as it has a long record of use and thus well-characterised cell lines and methods. This is despite the fact that the use of 2D culture is limiting due to its inability to capture in vivo-like cell-cell and cell-matrix interactions, and the fact many cell types display different phenotypes and varying genomic profiles in 2D versus 3D. Whilst the advantages of 3D cell culture are well understood, the reality is that many 3d culture systems can be challenging to reproduce to the levels required for HTS.
This is where 3D bioprintingis becoming recognised as a promising technology for HTS. It has the potential to produce more realistic, highly reproducible 3D cell cultures and support the bio-fabrication of 3D tissues and organoids.
The future of bioprinting in pharmaceutical applications
Bioprinting technology has advanced significantly in recent years, although it is still limited by the speed of printing and resolution. Therefore depending on the complexity of the printed construct, it may currently be a better candidate for use in lower throughput, larger scale models in 96-well or fewer plates. Nonetheless, in the future, with the advances being made in the precision, accuracy, and scale of the bioprinters, this technology might offer solutions for many current challenges of the drug development such as disease modelling, drug optimisation, toxicity screening and precision medicine.
- Disease modelling and drug optimization
Better disease models are crucial for better understanding the behaviour, development, treatment, prevention, and cure of disease. Bioprinting of 3D cell-hydrogel constructs, when combine with microfluidic systems, has allowed the creation of complex, reproducible organ-on-a-chip models which can replicate body wide diseases by incorporating many external features such as fluid or air flow and a combination of tissue types into a single 3d model. Such technology enables researchers to conduct disease progression studies for better understanding and ultimately treating the disease.
- Drug toxicity screening
When developing new drug treatments, toxic effects must be well characterised and monitored in vivo in animal models. The opportunity to more effectively model such effects prior to animal studies by utilising 3D cell culture models generated using bioprinting technology may allow for the drug to be modified or withdrawn prior to costly to in-vivo modelling.
One of the most heavily investigated side effects in drug development is the liver toxicity since it can result from over-exposure to toxins, leading to toxic hepatitis, inflammation of the liver, and eventual cirrhosis if exposed over a long period of time. These side effects further lead to what is known as drug-induced liver injury which is life-threatening. The complexity of the liver combined with the substantial role it plays in drug metabolism has created a demand for physiologically improved liver models which can be addressed by novel bioprinting approaches and improved liver models.
- Precision medicine
Precision medicine is the tailoring of therapy based on a patient’s genetic information. The use of a patient’s own cells allows for an amount of data to be collected for long term studies of disease progression and drug treatment response.
The use of 3D cell culture models in precision medicine allows for cells from the patient to be cultured and expanded to study the disease ex vivo while still maintaining in vivo genotype. Using the patient’s own cells, 3D bioprinting can be leveraged to create a large quantity of patient-specific disease models for use in parallel with clinical trials or independently through precision medicine initiatives for targeting patient or disease-specific genetic, proteomic, and phenotypic characteristics.
In summary, the potential of 3d bioprinting applications in high-throughput screening is vast, with drug screening and toxicity studies, disease modelling, and most recently precision medicine applications having a greater potential in the future due to the increased complexity, physiological relevance and reproducibility bioprinting can offer. By using bioprinting as a tool in high-throughput screening, physiologically relevant models can be realized for the improvement of healthcare.
Andrea Mazzocchi, Shay Soker, and Aleksander Skardal (2019) Applied Physics Reviews 6, 011302; https://doi.org/10.1063/1.5056188
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