Biomimetic 3D Tissue Models for Advanced High-Throughput Drug Screening

Abstract

Most current drug screening assays used to identify new drug candidates are 2D cell-based systems, even though such in vitro assays do not adequately recreate the in vivo complexity of 3D tissues. Inadequate representation of the human tissue environment during a preclinical test can result in inaccurate predictions of compound effects on overall tissue functionality. Screening for compound efficacy by focusing on a single pathway or protein target, coupled with difficulties in maintaining long-term 2D monolayers, can serve to exacerbate these issues when utilizing such simplistic model systems for physiological drug screening applications. Numerous studies have shown that cell responses to drugs in 3D culture are improved from those in 2D, with respect to modeling in vivo tissue functionality, which highlights the advantages of using 3D-based models for preclinical drug screens. In this review, we discuss the development of microengineered 3D tissue models which accurately mimic the physiological properties of native tissue samples, and highlight the advantages of using such 3D micro-tissue models over conventional cell-based assays for future drug screening applications. We also discuss biomimetic 3D environments, based-on engineered tissues as potential preclinical models for the development of more predictive drug screening assays for specific disease models.

3D bioprinting for engineering complex tissues

“…Compared to manual methods, bioprinting can deposit cells uniformly on the surface of micro devices. Such uniformity is highly desirable for testing and screening the interactions between cells and drugs (Huh and Kim 2015; Nam et al 2015). Existing examples of bioprinted drug testing platforms include those for the liver (Snyder et al 2011).…”

A guide to nanosafety testing: Considerations on cytotoxicity testing in different cell models

“…The use of complex cellular models has been discussed for some time as superior to the single layer dish culture (Guguen-Guillouzo et al 1983). For their use in toxicology it is expected that such models could yield more relevant data requiring less modelling or extrapolation (Nam et al 2015). Thereby, they are assumed to more reliably…”

Cell spheroids: the new frontiers in in vitro models for cancer drug validation

“…A number of innovative tissue-engineered methods to fabricate biomimetic Ewing's sarcoma tumors have been highlighted, emphasizing the role of the extracellular matrix and the surrounding cellular milieu and suggesting potential applications to improve our understanding of similar tumor biology, preclinical drug testing and personalized medicine [43]. Microengineered biomimetic 3D tissue models resemble the physiological properties of native tissues, having the advantages of potential preclinical models for the development of predictive drug screening assays in specific disease models [44], whereas interlockable microscaffolds fabricated by direct laser writing provide a tailor-made architecture for the encagement of cell spheroids suitable as in vitro model in several applications [45]. By means of simple spheroid technology based on an aqueous two-phase system [46], cancer cells confined in a drop of the denser aqueous dextran phase are robotically dispensed into microwells with the aqueous polyethylene glycol phase, forming viable spheroids, without a need for any external stimuli.…”