Advanced In Vitro Models for Biomedical Research: Technological progress towards physiological relevance and high throughput

Abstract

In vitro models are an indispensable tool for biomedical research due to their high levels of experimental control coupled with their reduction of animal testing which facilitates high levels of translatability of results to human patients. Traditional two-dimensional (2D) cell cultures fail to adequately reflect complex native environments due to a lack of cell-cell and cell-matrix interactions, coupled with the absence of waste and nutrient gradients. An ideal in vitro model is both physiologically relevant and facilitates high-throughput assessment. Numerous technological advances have progressed in vitro models in order to accommodate both of these characteristics, and these can be broadly categorized into (1) enhanced 3D culture techniques, (2) support systems and bioprinting, and (3) dynamic culture systems. The first technological category has allowed the recapitulation of 3D cell-cell interactions, as well as those between cells and their environment. The advent of support systems and bioprinting enables researchers to precisely integrate the ECM, a key native tissue component, into architecturally complex in vitro models. The final category encompasses the incorporation of dynamic microenvironments and biophysical stimuli in order to better resemble the dynamic nature of the human body. This review aims to highlight key publications which exemplify how these technological categories have enabled the next generation of in vitro models. The combination of these technologies may be the basis for achieving the “best of both” in terms of high throughput and high content models. Through this literature review, two techniques stand out due to their ability to encompass these aspects. Volumetric bioprinting and organ-on-a-chip technologies may therefore hold the keys for the future of advanced in vitro models.