In vitro models of the endocrine pancreas

Abstract

Ambitions to develop artificial tissue substitutes, combined with the need to study underlying mechanisms of disease under controlled conditions, shortcomings of animal models, as well as ethical constraints were the main driving forces behind the development of advanced in vitro models. These are defined as alternative experimental systems made by leveraging recent advances in tissue engineering and additive manufacturing that mimic tissue or organ level physiology in vitro. Simple in vitro models are already being used in many applications, however due to their many drawbacks, they incompletely mimic dynamic responses of native tissues. In order to construct functionally more relevant in vitro models, cells need to be grown in three-dimen-sional (3D) environments or bioscaffolds. Generally, bioscaffolds must recapitulate the microar-chitecture, hierarchical structure, physical properties, and composition of native tissues. None-theless, progress towards building more complex models is hindered primarily by the diffusion of gases and nutrients into the constructs´ interior. Currently, 3D printing presents the most promising solution for the production of advanced bioscaffolds which resolve the above men-tioned limitations. In addition to the technique´s ability to simultaneously use multiple biocom-patible materials, 3D printing enables material deposition with micrometer spatial resolution under cell-friendly conditions. The development of a functional in vitro pancreas model is gov-erned by the desire to study diabetes aetiology and is one of the main goals of the in vitro mod-elling domain, which to-date remains unfulfilled. The tissue slice method, despite having some drawbacks, presents the gold standard for basic and translational studies of the pancreas, while current most advanced 3D fabricated in vitro pancreas models mimic only basic functions of the organ. The purpose of this review is to provide an overview of in vitro models with a focus on in vitro models of the endocrine pancreas. We will highlight different model types and fundamental elements which need to be considered when constructing a model. Emphasis will be placed on more complex 3D fabricated in vitro models, tissue slices, bioscaffold material properties, and use of 3D printing for the fabrication of advanced bioscaffolds. We believe that simultaneous development of advanced materials, micro-manufacturing technologies, and advanced cell culture methods presents a very promising approach towards the construction of a functional in vitro pancreas model.