Operationalizing the Use of Biofabricated Tissue Models as Preclinical Screening Platforms for Drug Discovery and Development

Autor: Olive Jung, Marc Ferrer, Min Jae Song
Rok vydání: 2021
Předmět:
Zdroj: SLAS Discov
ISSN: 2472-5560
Popis: A wide range of complex in vitro models (CIVM) are being developed for scientific research and preclinical drug efficacy and safety testing. The hope is that these CIVMs will mimic human physiology and pathology and predict clinical responses more accurately than the cellular assays currently used. The integration of these CIVMs into the drug discovery and development pipeline requires rigorous scientific validation, including cellular, morphological, and functional characterization; benchmarking of clinical biomarkers; and operationalization as robust and reproducible screening platforms. It will be critical to establish the degree of physiological complexity that is needed in each CIVM to accurately reproduce native-like homeostasis and disease phenotypes, as well as clinical pharmacological responses. Choosing which CIVM to use at each stage of the drug discovery and development pipeline will be driven by a fit-per-purpose approach, based on the specific disease pathomechanism to model and screening throughput needed. Among the different CIVMs, biofabricated tissue equivalents are emerging as robust and versatile cellular assay platforms. Biofabrication technologies, including bioprinting approaches with hydrogels and biomaterials, have enables the production of tissues with a range of physiological complexity and controlled spatial arrangements in multi-well plate platforms, which make them amenable for medium throughput screening. However, operationalization of such 3D biofabricated models using existing automation screening platforms comes with a unique set of challenges. These challenges will be discussed in this perspective, including examples and thoughts coming from a laboratory dedicated to designing and developing assays for automated screening.
Databáze: OpenAIRE