Vascularized Lung Cancer Model for Evaluating the Promoted Transport of Anticancer Drugs and Immune Cells in an Engineered Tumor Microenvironment

Kim, Dasom; Hwang, Kyeong Seob; Seo, Eun U; Seo, Suyoung; Lee, Byung Chul; Choi, Nakwon; Choi, Jonghoon; Kim, Hong Nam

doi:10.1002/adhm.202102581

Cited by 34 publications

(39 citation statements)

References 60 publications

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“…One of the most common agents that determines the initiation of angiogenesis is Vascular Endothelial Growth Factor (VEGF) [ 39 , 40 ]. It has already been successfully used to initiate angiogenesis in microfluidics [ 20 , 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring Endothelial Expansion on a Chip

Konopka

Flont

Żuchowska

et al. 2022

Sensors

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Angiogenesis is the development of new blood vessels from the existing vasculature. Its malfunction leads to the development of cancers and cardiovascular diseases qualified by the WHO as a leading cause of death worldwide. A better understanding of mechanisms regulating physiological and pathological angiogenesis will potentially contribute to developing more effective treatments for those urgent issues. Therefore, the main goal of the following study was to design and manufacture an angiogenesis-on-a-chip microplatform, including cylindrical microvessels created by Viscous Finger Patterning (VFP) technique and seeded with HUVECs. While optimizing the VFP procedure, we have observed that lumen’s diameter decreases with a diminution of the droplet’s volume. The influence of Vascular Endothelial Growth Factor (VEGF) with a concentration of 5, 25, 50, and 100 ng/mL on the migration of HUVECs was assessed. VEGF’s solution with concentrations varying from 5 to 50 ng/mL reveals high angiogenic potential. The spatial arrangement of cells and their morphology were visualized by fluorescence and confocal microscopy. Migration of HUVECs toward loaded angiogenic stimuli has been initiated after overnight incubation. This research is the basis for developing more complex vascularized multi-organ-on-a-chip microsystems that could potentially be used for drug screening.

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Section: Discussionmentioning

confidence: 99%

Exploring Endothelial Expansion on a Chip

Konopka

Flont

Żuchowska

et al. 2022

Sensors

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“…The platform has potential in anticancer drug evaluation and clinical personalized medicine. Kim et al constructed a vascularized lung cancer model to assess the facilitated transport of anticancer drugs and immune cells in an engineered TME [ 130 ]. By controlling the interstitial flow direction, the presence and location of human lung fibroblasts, as well as the location of pulmonary cancer spheroids, are able to control the speed and direction of tumor angiogenesis.…”

Section: Ooc For Tumor Modelingmentioning

confidence: 99%

Recent Advances of Organ-on-a-Chip in Cancer Modeling Research

Liu

Zhang

et al. 2022

Biosensors

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Although many studies have focused on oncology and therapeutics in cancer, cancer remains one of the leading causes of death worldwide. Due to the unclear molecular mechanism and complex in vivo microenvironment of tumors, it is challenging to reveal the nature of cancer and develop effective therapeutics. Therefore, the development of new methods to explore the role of heterogeneous TME in individual patients’ cancer drug response is urgently needed and critical for the effective therapeutic management of cancer. The organ-on-chip (OoC) platform, which integrates the technology of 3D cell culture, tissue engineering, and microfluidics, is emerging as a new method to simulate the critical structures of the in vivo tumor microenvironment and functional characteristics. It overcomes the failure of traditional 2D/3D cell culture models and preclinical animal models to completely replicate the complex TME of human tumors. As a brand-new technology, OoC is of great significance for the realization of personalized treatment and the development of new drugs. This review discusses the recent advances of OoC in cancer biology studies. It focuses on the design principles of OoC devices and associated applications in cancer modeling. The challenges for the future development of this field are also summarized in this review. This review displays the broad applications of OoC technique and has reference value for oncology development.

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“… Kim et al (2022) inserted three needles of different diameters into their device, added a hydrogel composed of type I collagen and fibronectin, and removed the needles after gelation to create hollow channels inside the hydrogel. They seeded endothelial cells in the central channel, tumor cells on one side, and no cells on the other side to observe the effect of tumor cells on angiogenesis.…”

Section: Perfusion-ready Vessel Establishment In Tumor-on-a-chip Plat...mentioning

confidence: 99%

Tumor-on-a-chip: Perfusable vascular incorporation brings new approach to tumor metastasis research and drug development

Wang

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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The extracellular matrix interacts with cancer cells and is a key factor in the development of cancer. Traditional two-dimensional models cannot mimic the natural in situ environment of cancer tissues, whereas three-dimensional (3D) models such as spherical culture, bioprinting, and microfluidic approaches can achieve in vitro reproduction of certain structures and components of the tumor microenvironment, including simulation of the hypoxic environment of tumor tissue. However, the lack of a perfusable vascular network is a limitation of most 3D models. Solid tumor growth and metastasis require angiogenesis, and tumor models with microvascular networks have been developed to better understand underlying mechanisms. Tumor-on-a-chip technology combines the advantages of microfluidics and 3D cell culture technology for the simulation of tumor tissue complexity and characteristics. In this review, we summarize progress in constructing tumor-on-a-chip models with efficiently perfused vascular networks. We also discuss the applications of tumor-on-a-chip technology to studying the tumor microenvironment and drug development. Finally, we describe the creation of several common tumor models based on this technology to provide a deeper understanding and new insights into the design of vascularized cancer models. We believe that the tumor-on-a-chip approach is an important development that will provide further contributions to the field.

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Vascularized Lung Cancer Model for Evaluating the Promoted Transport of Anticancer Drugs and Immune Cells in an Engineered Tumor Microenvironment

Cited by 34 publications

References 60 publications

Exploring Endothelial Expansion on a Chip

Exploring Endothelial Expansion on a Chip

Recent Advances of Organ-on-a-Chip in Cancer Modeling Research

Tumor-on-a-chip: Perfusable vascular incorporation brings new approach to tumor metastasis research and drug development

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