A 3D Bioprinter Specifically Designed for the High-Throughput Production of Matrix-Embedded Multicellular Spheroids

Utama, Robert H.; Atapattu, Lakmali; O’Mahony, Aidan P.; Fife, Christopher M.; Baek, Je Hyun; Allard, Théophile; O’Mahony, Kieran J.; Ribeiro, Julio; Gaus, Katharina; Kavallaris, Maria; Gooding, J. Justin

doi:10.1016/j.isci.2020.101621

Cited by 63 publications

(60 citation statements)

References 36 publications

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“…In this process, a hydrogel bio-ink is deposited layer-by-layer and cell droplets are placed in the center of the hydrogel cup. Over time, the cells aggregate into spheroids 53 . The precise spheroid fabrication capacity of 3D printing has greatly aided spheroid research.…”

Section: Spheroid Fabrication Methodsmentioning

confidence: 99%

The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

et al. 2021

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A spheroid is a complex, spherical cellular aggregate supporting cell-cell and cell-matrix interactions in an environment that mimics the real-world situation. In terms of tissue engineering, spheroids are important building blocks that replace two-dimensional cell cultures. Spheroids replicate tissue physiological activities. The use of spheroids with/without scaffolds yields structures that engage in desired activities and replicate the complicated geometry of three-dimensional tissues. In this mini-review, we describe conventional and novel methods by which scaffold-free and scaffolded spheroids may be fabricated and discuss their applications in tissue regeneration and future perspectives.

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Section: Spheroid Fabrication Methodsmentioning

confidence: 99%

The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

et al. 2021

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“…Briefly, the authors proposed a bespoke drop-on-demand 3D bioprinter able to print a high density of cells in a single droplet directly into a hydrogel mold using a solenoid microvalve printhead. An alginate cup was firstly printed in a 96-well plate and then a cell-laden ink with 250 million cell/mL printed into the cup; inside the matrix, a combination of gravitational forces and ECM secretion by cells caused the formation of single embedded spheroid for each well in 24 h. Interestingly, as the cup was filled by the growing spheroid, the latter conformed to the shape of the cup confirming the bioprinter ability to controlled shape by matching cup size, cell volume and density in each droplet together with relevant tumor-like properties [ 44 ].…”

Section: Multicellular Spheroidsmentioning

confidence: 99%

“…Alternately, hydrogels as spheroids-embedding molds can help to control their size, rate of growth, drug responses and creating a more realistic model of in vivo situation [ 43 ]. For example, Utama et al [ 44 ] established a custom high-throughput bioprinting method for producing alginate and calcium chloride hydrogel-embedded spheroids of three different tumor cell lines (neuroblastoma, non-small cell lung cancer and glioblastoma cells) with controlled spatial distribution and size obtaining statistically reliable data in comparison to others research works. Briefly, the authors proposed a bespoke drop-on-demand 3D bioprinter able to print a high density of cells in a single droplet directly into a hydrogel mold using a solenoid microvalve printhead.…”

Section: Multicellular Spheroidsmentioning

confidence: 99%

Advanced Multi-Dimensional Cellular Models as Emerging Reality to Reproduce In Vitro the Human Body Complexity

Bassi

Grimaudo

Panseri

et al. 2021

IJMS

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A hot topic in biomedical science is the implementation of more predictive in vitro models of human tissues to significantly improve the knowledge of physiological or pathological process, drugs discovery and screening. Bidimensional (2D) culture systems still represent good high-throughput options for basic research. Unfortunately, these systems are not able to recapitulate the in vivo three-dimensional (3D) environment of native tissues, resulting in a poor in vitro–in vivo translation. In addition, intra-species differences limited the use of animal data for predicting human responses, increasing in vivo preclinical failures and ethical concerns. Dealing with these challenges, in vitro 3D technological approaches were recently bioengineered as promising platforms able to closely capture the complexity of in vivo normal/pathological tissues. Potentially, such systems could resemble tissue-specific extracellular matrix (ECM), cell–cell and cell–ECM interactions and specific cell biological responses to mechanical and physical/chemical properties of the matrix. In this context, this review presents the state of the art of the most advanced progresses of the last years. A special attention to the emerging technologies for the development of human 3D disease-relevant and physiological models, varying from cell self-assembly (i.e., multicellular spheroids and organoids) to the use of biomaterials and microfluidic devices has been given.

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“…In a very interesting study of R. Utama et al, the formation of matrix-embedded multicellular spheroids prepared in high-throughput (HTP) was described [ 96 ]. Authors developed an enabling technology consisting of a bespoke drop-on-demand 3D bioprinter capable of HTP printing of 96-well plates of spheroids.…”

Section: 3d Bioprintingmentioning

confidence: 99%

“…Additionally, the opportunity of HTP drug screening was investigated on neuroblastoma spheroids, exposed to doxorubicin. It was shown that sensitivity to spheroid size, embedding and how spheroids conform to the embedding affect the response toward doxorubicin [ 96 ].…”

Section: 3d Bioprintingmentioning

confidence: 99%

Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models

Ziółkowska-Suchanek

2021

Cells

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Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.

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A 3D Bioprinter Specifically Designed for the High-Throughput Production of Matrix-Embedded Multicellular Spheroids

Cited by 63 publications

References 36 publications

The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

Advanced Multi-Dimensional Cellular Models as Emerging Reality to Reproduce In Vitro the Human Body Complexity

Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models

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