AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.1413
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RESEARCH ARTICLE

Decellularized porcine kidney-incorporated hydrogels for cell-laden bioprinting of renal cell carcinoma model

Miaoben Wu1,2† ,  Hangyu Zhou2† ,  Jingying Hu2 ,  Zonghuan Wang3 ,  Yongqi Xu2 ,  Yibing Wu1 ,  Yang Xiang1 ,  Jun Yin4 ,  Peng Wei1 ,  Kailei Xu5,6* ,  Tiantian Ren7*
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1 Department of Plastic and reconstructive surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
2 Health Science Center, Ningbo University, Ningbo, Zhejiang, China
3 Department of Medical Research Center, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
4 The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, Zhejiang, China
5 Center for Medical and Engineering Innovation, Central Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
6 Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, China
7 Department of Trauma Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
IJB 2024, 10(2), 1413 https://doi.org/10.36922/ijb.1413
Submitted: 29 July 2023 | Accepted: 18 October 2023 | Published: 12 January 2024
(This article belongs to the Special Issue 3D Bioprinting for Tumor Modeling)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

More than 90% of kidney cancers are attributed to renal cell carcinoma (RCC), which is however highly resistant to traditional chemotherapy. The challenges met in treating RCC signify an imperative to accelerate the development of new and effective drugs. Preclinical testing has served as a foundation for evaluating potential effectiveness of new drugs, but this endeavor is deeply restricted by the current generation of in vitro two-dimensional culture models, which cannot accurately mimic the tumor microenvironment (TME). Therefore, new in vitro three-dimensional (3D) cell culture models that can better mimic the components and architecture of TME have been developed for preclinical testing, but only a few existing 3D cell culture models can simulate the TME of RCC, representing a limitative obstacle impeding the development of novel drugs for RCC. In this study, we prepared a bioink by mixing porcine kidney decellularized extracellular matrix (dECM) powders with gelatin methacryloyl (GelMA) to bioprint an in vitro 3D cell culture model for RCC. We found that GelMA stability, mechanical properties, and printability were all significantly improved following the addition of the dECM powder. Moreover, cell cultures using ACHN cells suggested that kidney dECM powders significantly improved the cellular proliferation and metastasis via upregulation of markers related to epithelial– mesenchymal transition, along with activation of several cancer progression-related signaling pathways. More importantly, ACHN cells also demonstrated higher resistance to sunitinib under the stimulation of kidney dECM, indicating that GelMA-kidney dECM hydrogels may be an appropriate preclinical model to be used for building an in vitro RCC platform for drug screening and development.

Keywords
Tumor microenvironment
Gelatin methacrylate
3D culture
Tumor model
Drug screening
Funding
This study was partly funded by the National Natural Science Foundation of China (Grant No. 12202387), the Natural Science Foundation of Zhejiang Province (Grant No. BY23H180015), the Natural Science Foundation of Ningbo (Grant Nos. 2022J216, 2022J212), the Foundation of Ningbo Science and Technology Bureau (Grant No. 2023Z193), Ningbo Medical Science and Technology Program (Grant No. 2020Y73), and the Zhejiang Medical Science and Technology Project (Grant No. 2020KY825).
Conflict of interest
The authors declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position of the authors in this paper.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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