Cell–extracellular matrix mechanotransduction in 3D

Saraswathibhatla, Aashrith; Indana, Dhiraj; Chaudhuri, Ovijit

doi:10.1038/s41580-023-00583-1

Cited by 94 publications

(34 citation statements)

References 292 publications

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“…Moreover, tumor microenvironments are shaped by “tumor stroma”, which mainly consists of the basement membrane, fibroblasts, immune cells, and vasculature. Each component is indispensable for the reproduction of the “in vivo situation” of a tumor, which affects the differentiation, proliferation, invasion, and metastasis of cancer cells [ 165 ].…”

Section: Imaging and Analysis Of Mctsmentioning

confidence: 99%

Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis

Mitrakas

Tsolou

Didaskalou

et al. 2023

IJMS

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Biomedical research requires both in vitro and in vivo studies in order to explore disease processes or drug interactions. Foundational investigations have been performed at the cellular level using two-dimensional cultures as the gold-standard method since the early 20th century. However, three-dimensional (3D) cultures have emerged as a new tool for tissue modeling over the last few years, bridging the gap between in vitro and animal model studies. Cancer has been a worldwide challenge for the biomedical community due to its high morbidity and mortality rates. Various methods have been developed to produce multicellular tumor spheroids (MCTSs), including scaffold-free and scaffold-based structures, which usually depend on the demands of the cells used and the related biological question. MCTSs are increasingly utilized in studies involving cancer cell metabolism and cell cycle defects. These studies produce massive amounts of data, which demand elaborate and complex tools for thorough analysis. In this review, we discuss the advantages and disadvantages of several up-to-date methods used to construct MCTSs. In addition, we also present advanced methods for analyzing MCTS features. As MCTSs more closely mimic the in vivo tumor environment, compared to 2D monolayers, they can evolve to be an appealing model for in vitro tumor biology studies.

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Section: Imaging and Analysis Of Mctsmentioning

confidence: 99%

Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis

Mitrakas

Tsolou

Didaskalou

et al. 2023

IJMS

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“…Cells cultured in two dimensions (2D) failed to recapitulate the normal cell morphology and interactions in vivo. Isolated tissue cells cultured in a 2D system gradually lose their morphology and become flattened, abnormally divided, and influence the cellular differentiated phenotype 21,22 . 2D attachment tends to cause cells to lose their original shape and hierarchical structure and affect cell–cell and cell–extracellular signal transduction and interactions, resulting in cells that do not properly reproduce the cellular functions and behaviors present in tissues or organs 23 .…”

Section: Introductionmentioning

confidence: 99%

Organoids: The current status and biomedical applications

Yang

Kung

et al. 2023

MedComm

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Organoids are three‐dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self‐organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long‐term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large‐scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.

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“…The mechanical properties of hydrogels have a significant impact on their ability to mimic the natural ECM environment. 15 For example, hydrogels with high cross-linking density are suitable for rigid tissues like cartilage or bone, whereas low cross-linking density hydrogels are better suited for flexible tissues such as skin or blood vessels. Tissues in the human body, such as the breast, brain, heart, kidney, arterial wall, and vein, exhibit a diverse range of elastic moduli (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Optimization of Gelatin Methacryloyl Hydrogel Properties through an Artificial Neural Network Model

Karaoglu,

Kebabci,

Kizilel

2023

ACS Appl. Mater. Interfaces

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Gelatin methacryloyl (GelMA) hydrogels are promising materials for tissue engineering applications due to their biocompatibility and tunable properties. However, the time-consuming process of preparing GelMA hydrogels with desirable properties for specific biomedical applications limits their clinical use. Visible-light-induced cross-linking is a well-known method for the preparation of GelMA hydrogels; however, a comprehensive investigation on the influence of critical parameters such as Eosin Y (EY), triethanolamine (TEA), and N-vinyl-2-pyrrolidone (NVP) concentrations on the stiffness and gelation time has yet to be performed. In this study, we systematically investigated the effect of these critical parameters on the stiffness and gelation time of GelMA hydrogels. We developed an artificial neural network (ANN) model with three input variables, EY, TEA, and NVP concentrations, and two output variables, Young’s modulus and gelation time, derived from our experimental design. Through the alteration of individual chemical concentrations, [EY] between 0.005 and 0.5 mM and [TEA] and [NVP] between 10 and 1000 mM, we studied the impact of these alterations on the real-time values of stiffness and gelation time. Furthermore, we demonstrated the validity of the ANN model in predicting the properties of GelMA hydrogels. We also studied cell survival to establish nontoxic concentration ranges for each component, enabling safer use of GelMA hydrogels in relevant biomedical applications. Our results showed that the ANN model can accurately predict the properties of GelMA hydrogels, allowing for the synthesis of hydrogels with desirable stiffness for various biomedical applications. In conclusion, our study provides a comprehensive library that characterizes the stiffness and gelation time and demonstrates the potential of the ANN model to predict these properties of GelMA hydrogels depending on the critical parameters. The ANN models developed here can facilitate the optimization of GelMA hydrogels with the most efficient mechanical properties that resemble a native extracellular matrix and better address the need in the in vivo microenvironment. The approach of this study is to bring research about the synthesis of GelMA hydrogels to a new level where the synthesis of these hydrogels can be standardized with minimum cost and effort.

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Cell–extracellular matrix mechanotransduction in 3D

Cited by 94 publications

References 292 publications

Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis

Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis

Organoids: The current status and biomedical applications

Optimization of Gelatin Methacryloyl Hydrogel Properties through an Artificial Neural Network Model

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