Abstract

The re-creation of physiological cellular microenvironments that truly resemble complex in vivo architectures is the key aspect in the development of advanced in vitro organotypic tissue constructs. Among others, organ-on-a-chip technology has been increasingly used in recent years to create improved models for organs and tissues in human health and disease, because of its ability to provide spatio-temporal control over soluble cues, biophysical signals and biomechanical forces necessary to maintain proper organotypic functions. While media supply and waste removal are controlled by microfluidic channel by a network the formation of tissue-like architectures in designated micro-structured hydrogel compartments is commonly achieved by cellular self-assembly and intrinsic biological reorganization mechanisms. The recent combination of organ-on-a-chip technology with three-dimensional (3D) bioprinting and additive manufacturing techniques allows for an unprecedented control over tissue structures with the ability to also generate anisotropic constructs as often seen in in vivo tissue architectures. This review highlights progress made in bioprinting applications for organ-on-a-chip technology, and discusses synergies and limitations between organ-on-a-chip technology and 3D bioprinting in the creation of next generation biomimetic in vitro tissue models.

Highlights

  • The homeostasis and proper function of complex living biological structures such as organs and tissues are guided the interplay between cell communication, tissue composition and architecture governs development, repair andfunction

  • Advanced microfluidic tissue-like models called microphysiological/organ-on-a-chip systems have shown the ability to control both intra and inter-cellular communication processes as well as providing necessary architectural features seen in living tissue and organs (Ergir et al, 2018; Kratz et al, 2019b)

  • A variety of advanced three-dimensional (3D) cell culture techniques have been implemented in organ-ona-chip systems such as hanging drop spheroids, hydrogel microtissues und matrix-free self-assembled organoids inside microfluidic channel networks to precisely control the cellular microenvironment with high temporal and spatial resolution (Ling et al, 2007; Frey et al, 2014; Yu et al, 2019)

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Summary

INTRODUCTION

The homeostasis and proper function of complex living biological structures such as organs and tissues are guided the interplay between cell communication, tissue composition and architecture governs development, repair and (dys)function. Based on spheroidal self-assembly and lumen generation Tröndle et al (Tröndle et al, 2021) reported inkjet printing of cell aggregates to fabricate a perfused tubular structure using a layer-by-layer approach similar to the renal model by Homan and colleagues mentioned in the previous section on extrusion-based systems (see Figures 3A,B). Perfusable and mechanically stable hydrogel structures in self-containing chips featuring vascularlike networks were printed at high-resolution from poly (ethylene glycol) diacrylate (PEGDA, MW 700) hydrogel This vascular system with a cross-section down to 100 μm × 100 μm was steadily perfusable for more native tissue-like dynamic culture of human umbilical-vein endothelial cells (HUVEC) after 7 days post-seeding. Another high-resolution biomimetic approach was TABLE 1 | Overview of (bio)printing methods for organ-on-a-chip applications

Extrusion shear
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