3D bioprinting for drug discovery and development in pharmaceutics.

Successful launch of a commercial drug requires significant investment of time and financial resources wherein late-stage failures become a reason for catastrophic failures in drug discovery. This calls for infusing constant innovations in technologies, which can give reliable prediction of efficacy, and more importantly, toxicology of the compound early in the drug discovery process before clinical trials. Though computational advances have resulted in more rationale in silico designing, in vitro experimental studies still require gaining industry confidence and improving in vitro-in vivo correlations. In this quest, due to their ability to mimic the spatial and chemical attributes of native tissues, three-dimensional (3D) tissue models have now proven to provide better results for drug screening compared to traditional two-dimensional (2D) models. However, in vitro fabrication of living tissues has remained a bottleneck in realizing the full potential of 3D models. Recent advances in bioprinting provide a valuable tool to fabricate biomimetic constructs, which can be applied in different stages of drug discovery research. This paper presents the first comprehensive review of bioprinting techniques applied for fabrication of 3D tissue models for pharmaceutical studies. A comparative evaluation of different bioprinting modalities is performed to assess the performance and ability of fabricating 3D tissue models for pharmaceutical use as the critical selection of bioprinting modalities indeed plays a crucial role in efficacy and toxicology testing of drugs and accelerates the drug development cycle. In addition, limitations with current tissue models are discussed thoroughly and future prospects of the role of bioprinting in pharmaceutics are provided to the reader.

STATEMENT OF SIGNIFICANCE: Present advances in tissue biofabrication have crucial role to play in aiding the pharmaceutical development process achieve its objectives. Advent of three-dimensional (3D) models, in particular, is viewed with immense interest by the community due to their ability to mimic in vivo hierarchical tissue architecture and heterogeneous composition. Successful realization of 3D models will not only provide greater in vitro-in vivo correlation compared to the two-dimensional (2D) models, but also eventually replace pre-clinical animal testing, which has their own shortcomings. Amongst all fabrication techniques, bioprinting- comprising all the different modalities (extrusion-, droplet- and laser-based bioprinting), is emerging as the most viable fabrication technique to create the biomimetic tissue constructs. Notwithstanding the interest in bioprinting by the pharmaceutical development researchers, it can be seen that there is a limited availability of comparative literature which can guide the proper selection of bioprinting processes and associated considerations, such as the bioink selection for a particular pharmaceutical study. Thus, this work emphasizes these aspects of bioprinting and presents them in perspective of differential requirements of different pharmaceutical studies like in vitro predictive toxicology, high-throughput screening, drug delivery and tissue-specific efficacies. Moreover, since bioprinting techniques are mostly applied in regenerative medicine and tissue engineering, a comparative analysis of similarities and differences are also expounded to help researchers make informed decisions based on contemporary literature.