3D vascularized microphysiological system for investigation of tumor-endothelial crosstalk in anti-cancer drug resistance

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Despite the advantages of microfluidic system in drug screening, vascular systems responsible for the transport of drugs and nutrients have been hardly considered in the microfluidic-based chemotherapeutic screening. Considering the physiological characteristics of highly vascularized urinary tumors, we here investigated the chemotherapeutic response of bladder tumor cells using a vascularized tumor on a chip. The microfluidic chip was designed to have open-top region for tumor sample introduction and hydrophilic rail for spontaneous hydrogel patterning, which contributed to the construction of tumor-hydrogel-endothelium interfaces in a spatiotemporal on-demand manner. Utilizing the chip where intravascularly injected cisplatin diffuse across the endothelium and transport into tumor samples, chemotherapeutic responses of cisplatin-resistant or -susceptible bladder tumor cells were evaluated, showing the preservation of cellular drug resistance even within the chip. The open-top structure also enabled the direct harvest of tumor samples and post analysis in terms of secretome and gene expressions. Comparing the cisplatin efficacy of the cisplatin-resistant tumor cells in the presence or absence of endothelium, we found that the proliferation rates of tumor cells were increased in the vasculature-incorporated chip. These have suggested that our vascularized tumor chip allows the establishment of vascular-gel-tumor interfaces in spatiotemporal manners and further enables investigations of chemotherapeutic screening.
Publisher
IOP Publishing Ltd
Issue Date
2023-10
Language
English
Article Type
Article
Citation

BIOFABRICATION, v.15, no.4

ISSN
1758-5082
DOI
10.1088/1758-5090/acef99
URI
http://hdl.handle.net/10203/312152
Appears in Collection
ME-Journal Papers(저널논문)
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