A Highly Reproducible Micro U‐Well Array Plate Facilitating High‐Throughput Tumor Spheroid Culture and Drug Assessment

Wu, Kuang‐Wei; Kuo, Cheng-Tzu; Tu, Ting‐Yuan

doi:10.1002/gch2.202000056

Cited by 14 publications

(13 citation statements)

References 36 publications

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“…After adding the HEPES-based saline solution and placing the microelectrode and reference electrode in the well, the tip was scanned above the chip surface to detect the oxygen concentration. The microwell arrays method has been widely used in the preparation of spheroids [ 7 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Methods For Mcss Generationmentioning

confidence: 99%

Recent Advances in Three-Dimensional Multicellular Spheroid Culture and Future Development

Shen

Cai

et al. 2021

Micromachines

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Three-dimensional multicellular spheroids (MCSs) have received extensive attention in the field of biomedicine due to their ability to simulate the structure and function of tissues in vivo more accurately than traditional in vitro two-dimensional models and to simulate cell–cell and cell extracellular matrix (ECM) interactions. It has become an important in vitro three-dimensional model for tumor research, high-throughput drug screening, tissue engineering, and basic biology research. In the review, we first summarize methods for MCSs generation and their respective advantages and disadvantages and highlight the advances of hydrogel and microfluidic systems in the generation of spheroids. Then, we look at the application of MCSs in cancer research and other aspects. Finally, we discuss the development direction and prospects of MCSs

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Section: Methods For Mcss Generationmentioning

confidence: 99%

Recent Advances in Three-Dimensional Multicellular Spheroid Culture and Future Development

Shen

Cai

et al. 2021

Micromachines

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“…The exact shapes of the microwells and the relationship between laser speed and the depth of microwells are illustrated in Figure B. At higher engraving speeds, the engraving depth reduces as the laser beam spends less time at each point, resulting in less heat absorption by the material and a shallower and narrower microchannel. − …”

Section: Resultsmentioning

confidence: 99%

Simple and Rapid Method of Microwell Array Fabrication for Drug Testing on 3D Cancer Spheroids

Nguyen,

Dinh,

Do Thi

et al. 2024

ACS Omega

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Three-dimensional (3D) cell culture systems are becoming increasingly popular due to their ability to mimic the complex process of angiogenesis in cancer, providing more accurate and physiologically relevant data than traditional twodimensional (2D) cell culture systems. Microwell systems are particularly useful in this context as they provide a microenvironment that more closely resembles the in vivo environment than traditional microwells. Poly(ethylene glycol) (PEG) microwells are particularly advantageous due to their bio-inertness and the ability to tailor their material characteristics depending on the PEG molecular weight. Although there are several methods available for microwell fabrication, most of them are time-consuming and expensive. The current study utilizes a low-cost laser etching technique on poly(methyl methacrylate) materials followed by molding with PDMS to produce microwells. The optimal conditions for making concave microwells are an engraving parameter speed of 600 mm/s, power of 20%, and a design diameter of the microwell of 0.4 mm. The artificial tumor achieved its full size after 7 days of cell growth in a microwell system, and the cells developed drugs through a live/dead assay test. The results of the drug testing revealed that the IC 50 value of zerumbone-loaded liposomes in HepG2 was 4.53 pM, which is greater than the IC 50 value of zerumbone. The HepG2 cancer sphere's 3D platform for medication testing revealed that zerumbone-loaded liposomes were very effective at high doses. These findings generally imply that zerumbone-loaded liposomes have the capacity to target the liver and maintain medication delivery.

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“…Consequently, we believe that more effective and meaningful results can be obtained regarding drug response against aggressive tumor tissue with drug resistance by inducing motility in cancer cells by utilizing this macroscale dense 3D MCTs-ECM tumor graft than the MCTs model. Furthermore, our simple experimental method for the fabrication of macroscale 3D in vitro grafts presented in this study is also expected methodologically because it can be applied to the platform such as a microwell array shown in Wu's recent research [60].…”

Section: Discussionmentioning

confidence: 98%

Sporadic cell death in macroscale 3D tumor grafts with high drug resistance by activating cell-ECM interactions

2021

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In the tumor microenvironment (TME), the extracellular matrix (ECM) provides a dynamic structure for cell adhesion and cancer cell motility, such as migration and invasion, as well as remodeling. Matrix metalloproteinases (MMPs) promote cancer cell motility, which contributes to inducing drug resistance and thereby acquiring aggressive features. The drug resistance-induced 3D in vitro tumor model can be an effective model for therapeutic strategies for anticancer drugs targeting aggressive cancer cells. Here, we describe highly drug-resistant multicellular tumoroids (MCTs)-ECM tumor grafts under a macroscale dense 3D in vitro model through a combination of numerous MCTs and a collagen matrix. MCTs-ECM tumor grafts promote the high activity of MMP2 and MMP9 compared to general MCTs and induced cancer cell motility. Then, after the administration of anticancer drugs, the tumor grafts show increased drug resistance, with both the sporadic distribution of necrotic cells and the reduction of apoptotic portions, by activating cancer cell motility. MCTs-ECM tumor graft could be useful as a macroscale tumor graft model for inducing drug resistance by activating cancer cell motility and evaluating the efficacy of anticancer drugs targeting cancer with aggressive features.

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A Highly Reproducible Micro U‐Well Array Plate Facilitating High‐Throughput Tumor Spheroid Culture and Drug Assessment

Cited by 14 publications

References 36 publications

Recent Advances in Three-Dimensional Multicellular Spheroid Culture and Future Development

Recent Advances in Three-Dimensional Multicellular Spheroid Culture and Future Development

Simple and Rapid Method of Microwell Array Fabrication for Drug Testing on 3D Cancer Spheroids

Sporadic cell death in macroscale 3D tumor grafts with high drug resistance by activating cell-ECM interactions

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