3D organ models-Revolution in pharmacological research?

Abstract

3D organ models have gained increasing attention as novel preclinical test systems and alternatives to animal testing. Over the years, many excellent in vitro tissue models have been developed. In parallel, microfluidic organ-on-a-chip tissue cultures have gained increasing interest for their ability to house several organ models on a single device and interlink these within a human-like environment. In contrast to these advancements, the development of human disease models is still in its infancy. Although major advances have recently been made, efforts still need to be intensified. Human disease models have proven valuable for their ability to closely mimic disease patterns in vitro, permitting the study of pathophysiological features and new treatment options. Although animal studies remain the gold standard for preclinical testing, they have major drawbacks such as high cost and ongoing controversy over their predictive value for several human conditions. Moreover, there is growing political and social pressure to develop alternatives to animal models, clearly promoting the search for valid, cost-efficient and easy-to-handle systems lacking interspecies-related differences. In this review, we discuss the current state of the art regarding 3D organ as well as the opportunities, limitations and future implications of their use.

Keywords: 3D printing; Alternatives to animal testing; Excised human tissue; Organ model; Pharmacological testing in vitro; Tissue engineering.

Graphical abstract

Fig. 1

Chances and limitations of 3D organ and animal models in drug development.

Fig. 2

Overview of different approaches towards 3D organ models.

Fig. 3

Brightfield micrographs of 3D printed and manually seeded paraffin embedded histological cross sections of a 2 layered air-blood barrier model stained with Masson-Goldner trichrome coloration after 3 days in culture. Cytoplasm is stained red, collagen fibers of the ECM Matrigel^™ green and cell nuclei dark brown. Note the lack of cell organization in the manually seeded compared to the bioprinted model. Scale bars 100 μm. Reproduced in accordance with the Creative Commons Public License (http://creativecommons.org/licenses/by-nc-nd/4.0/) from [34]. Copyright 2015, Springer Nature. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).