Evolution of toxicity testing platforms from 2D to advanced 3D bioprinting for safety assessment of drugs

Abstract

The process involved in the discovery of novel drugs in medical sciences is challenging due to the time-intensive process that results in a high cost of development. Additionally, it is reported that 90 % of new drugs fail in clinical trials and cannot reach the market. One of the primary reasons for failure is that research laboratories and pharmaceutical companies have been relying exclusively on data derived from animal-based models for testing the efficacy and safety of newly developed drugs. These models do not completely recapitulate human physiology or pathophysiology, resulting in a lower translational rate. Further, the evaluation of toxicity of drugs to the human body requires a more robust and holistic approach. Researchers across the globe are focusing on developing in vitro3D models as alternatives to traditional animal testing to circumvent these challenges. These model systems could replicate and mimic the human physiological microenvironment, cellular interactions, and arrangements. In vitro3D models would provide improved methods to evaluate and comprehend drug response, thereby reducing the burden on animal usage. Further, reducing the time and costs associated with developing, screening, drug failure, and translation of drugs is also realizable. In this communication, existing in vitro 3D models that are used in the drug development process are reviewed. In addition, the advancements in using 3D bioprinting and organ-on-a-chip technologies towards generating human reconstructed tissues/organs are also highlighted. The challenges from a technological and regulatory perspective on adapting these alternate animal models are also discussed.