3D Miniaturization of Human Organs for Drug Discovery

Abstract

“Engineered human organs” hold promises for predicting the effectiveness and accuracy of drug responses while reducing cost, time, and failure rates in clinical trials. Multiorgan human models utilize many aspects of currently available technologies including self‐organized spherical 3D human organoids, microfabricated 3D human organ chips, and 3D bioprinted human organ constructs to mimic key structural and functional properties of human organs. They enable precise control of multicellular activities, extracellular matrix (ECM) compositions, spatial distributions of cells, architectural organizations of ECM, and environmental cues. Thus, engineered human organs can provide the microstructures and biological functions of target organs and advantageously substitute multiscaled drug‐testing platforms including the current in vitro molecular assays, cell platforms, and in vivo models. This review provides an overview of advanced innovative designs based on the three main technologies used for organ construction leading to single and multiorgan systems useable for drug development. Current technological challenges and future perspectives are also discussed.

Drug screening model meets cancer organoid technology

“…On the other hand, as the tumor organoids lost their original arrangement style, it was necessary to develop new technology such as scaffolds, 3D printing technology, and air-liquid interface, which facilitated tumor organoids form similar structures to primary tumor tissues. 3D printing technology had been used to construct an engineered organ, which enabled the organ to complete the spatial arrangement of cells, the composition of ECM, and the multicellular activity [ 103 , 104 ]. In 3D scaffolds, cancer cells and endothelial cells were co-cultured, a vascular structure could be formed by using microfluidic technology [ 105 ].…”

A 3D Printed Hanging Drop Dripper for Tumor Spheroids Analysis Without Recovery

“…Conventional approaches to produce cell aggregates, including culturing cell in stirring suspension 11 , round bottom non-adherent plate 12 , by magnetic levitation 13 , and hanging drop 14 , are hampered by the limitations like the variation in spheroids size, cell number, labor-intensive, high-shear force, and difficulties on massive production 15 . Recently, some microfabrication based methods, such as microwell 16–18 , microfluidics 19,20 , and microfabricated hanging drop 21–23 , have gained lots of attention due to the formation of a large amount of well-controlled aggregates with uniform size, less laborious, and amenable to high throughput screening 24 . However, to produce such platforms, expensive and time-consuming photolithography or micro-molding fabrication is still an indispensable requisite in those methodologies, and thus are closed-source technologies and not a cost-effective way to perform a micro tissue-based assay.…”

Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays

“…Organoids can also be generated from patients with various pathological conditions, such as inflammatory bowel disease or from individuals with various genetic backgrounds (Dekkers et al 2013;VanDussen et al 2015). Organoids from individuals with cells of varying genetic make-up opens a plethora of possibilities for designing of idiosyncratic therapies and personalized medicine (reviewed in Park et al 2018;Lehle et al 2019). Nonetheless, there are disadvantages associated with the physical organization of organoids.…”

In Vitro Tissue‐Engineered Skeletal Muscle Models for Studying Muscle Physiology and Disease

“…For several decades cell culture models have been used in drug screening assays to identify novel therapeutic candidates, which were then tested in small and large animal models. However, only 10% of drugs that pass preclinical animal tests are eventually used clinically due to unforeseen drug toxicity or insufficient therapeutic benefits, resulting in an average drug development cost of≈1 billion dollars [8,251,252] Culturing human cancer cells in a 3D microenvironment has been shown to yield more predictive drug screening assays than use of 2D cultures or animal models, suggesting that 3D human tissue models may be able to better model clinical drug responses [253,254] For skeletal muscle, desired drug response would likely include improved contractile function and/or tissue regeneration. In 2D cultures, these outcomes can only be measured indirectly via expression of differentiation marker levels, fusion index, or cell viability.…”

A H2O2-Responsive Boron Dipyrromethene-Based Photosensitizer for Imaging-Guided Photodynamic Therapy

“…Photodynamic therapy (PDT) has received great attention for their advantages such as minimal invasiveness, high selectivity and low immunogenicity [1,2]. The method involves three elements: near-infrared light, molecular oxygen and photosensitizers, which can generate cytotoxic reactive oxygen species (ROS) in tumors region to induce cancer cells apoptosis and necrosis [3].…”