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DLM-GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing

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机构: [1]Department of Respiratory and Critical Care Medicine, Provincial Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu, 610065, People's Republic of China [2]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China. [3]College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China. [4]Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu, 641400, China. [5]Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 999077, China. [6]Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China. [7]Sichuan Diya BioTechnology Group Company, Chengdu, 641400, China. [8]Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. [9]Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China. [10]Research Institute for Intelligent Wearable Systems, the Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 999077, China.
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摘要:
The in vitro recapitulation of tumor microenvironment is of great interest to preclinical screening of drugs. Compared with culture of cell lines, tumor organ slices can better preserve the complex tumor architecture and phenotypic activity of native cells, but are limited by their exposure to fluid shear and gradual degradation under perfusion culture. Here, we established a decellularized liver matrix (DLM)-GelMA "sandwich" structure and a perfusion-based microfluidic platform to support long-term culture of tumor slices with excellent structural integrity and cell viability over 7 days. The DLM-GelMA was able to secrete cytokines and growth factors while providing shear protection to the tumor slice via the sandwich structure, leading to the preservation of the tumor microenvironment where immune cells (CD3, CD8, CD68), tumor-associated fibroblasts (α-SMA), and extracellular matrix components (collagen I, fibronectin) were well maintained. Furthermore, this chip presented anti-tumor efficacy at cisplatin (20 μM) on tumor patients, demonstrating our platform's efficacy to design patient-specific treatment regimens. Taken together, the successful development of this DLM-GelMA sandwich structure on the chip could faithfully reflect the tumor microenvironment and immune response, accelerating the screening process of drug molecules and providing insights for practical medicine.

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出版当年[2023]版:
大类 | 2 区 工程技术
小类 | 1 区 生化研究方法 1 区 分析化学 2 区 化学:综合 2 区 仪器仪表 2 区 纳米科技
最新[2023]版:
大类 | 2 区 工程技术
小类 | 1 区 生化研究方法 1 区 分析化学 2 区 化学:综合 2 区 仪器仪表 2 区 纳米科技
第一作者:
第一作者机构: [1]Department of Respiratory and Critical Care Medicine, Provincial Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu, 610065, People's Republic of China [2]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China. [3]College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China. [4]Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu, 641400, China.
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通讯作者:
通讯机构: [1]Department of Respiratory and Critical Care Medicine, Provincial Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu, 610065, People's Republic of China [2]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China. [3]College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China. [4]Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu, 641400, China. [5]Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 999077, China. [10]Research Institute for Intelligent Wearable Systems, the Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 999077, China.
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