3-D bioprinted tissues as disease-in-a-dish models for drug screening
More than 90% of drugs that enter clinical evaluation fail to reach approval because of lack of efficacy or unexpected toxicity. This failure rate is in large part due to the use of overly simplistic in-vitro cell-based assays and animal models with limited predictive value…
As knowledge of cellular processes in humans and research technologies have improved, it has become more apparent that the complexity of cellular pathways, disease-relevant cellular backgrounds, cell-cell interactions, and cellular-microenvironment interactions in tissues are critical for the understanding of drug efficacy and toxicity in humans, and are considerations that need to be integrated into future drug discovery in vitro cell-based assays.
Three-dimensional (3-D) cell cultures that mimic the spatial organisation of cells in a live tissue in vivo are now being developed to test the activity of therapeutics in possibly more predictive assay systems. These 3-D culture models range from spheres and organoids to bioprinted tissues. Here, we discuss the use of 3-D tissue models for drug screening and, in particular, the use of 3-D bioprinting to fabricate such tissues from the perspective of a laboratory focused on drug screening and discovery.
3-D bioprinting is the process of producing spatially-controlled patterns of functionally viable tissue-relevant cells using a bioprinter. The application of 3-D bioprinting to tissue repair and regenerative medicine to replace damaged tissues and organs has fuelled the recent interest in this field of tissue engineering.3-6 In addition, 3-D bioprinting of human tissues carries the potential to accelerate the drug discovery process by bridging the predictability gap between in vitro and in vivo assay systems and positive clinical outcomes.7-11 The added promise of these 3-D tissue models is that they will reduce animal testing, and perhaps in the future eliminate animal testing, expedite drug development, enhance experimentation capabilities, and save valuable time and funding.
3-D tissue bioprinting promises to address these challenges by integrating five recently emerging technologies:
- 3D bioprinters are now available with precise XYZ alignment to reproducibly fabricate tissues with defined threedimensional geometries
- Biomaterial and biocompatible hydrogels are being developed to support the threedimensional structures of cell assemblies comprising the tissue
- It is also now possible to obtain autologous cells from patients using human induced pluripotent stem cells (hiPSCs) and relevant differentiation protocols, and streamlined processes are being developed to scale up their production
- Microtiter plates are now being designed that enable the delivery of nutrients, mechanical, and chemical cues to the cells seeded in the printed tissues
- The ability to quantitatively characterise the morphology and functionality of printed tissues is also now starting to be possible using both invasive and non-invasive technologies.
National Center for Advancing Translational Sciences' (NCATS)