兼具可打印性及生物相容性的水凝胶用于无残留打印高通量的患者来源类器官生物芯片

Printable and biocompatible hydrogels for residual-free and high-throughput printing patient-derived organoid biochips

谢岱希 ¹陈炳达 ²薛勇敢 ³孙志远 ⁴宁伯彬 ³张泽英 ²迟基梅 ¹苏萌 ¹宋延林¹

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作者信息

1. Key Laboratory of Green Printing,Institute of Chemistry,Chinese Academy of Sciences,Beijing Engineering Research Center of Nanomaterials for Green Printing Technology,Beijing National Laboratory for Molecular Sciences(BNLMS),Beijing 100190,China;University of Chinese Academy of Sciences,Beijing 100049,China
2. Key Laboratory of Green Printing,Institute of Chemistry,Chinese Academy of Sciences,Beijing Engineering Research Center of Nanomaterials for Green Printing Technology,Beijing National Laboratory for Molecular Sciences(BNLMS),Beijing 100190,China
3. Department of General Surgery,The First Medical Centre,Chinese PLA General Hospital,Beijing 100853,China
4. School of Chemical Engineering and Technology,Xi'an Jiaotong University,Xi'an,710049,China
折叠

摘要

类器官生物芯片可以模拟真实人体器官的微环境和功能特征,为疾病建模和药物筛选提供了新的平台.但传统手工培养类器官及构建生物芯片的方法通常过程复杂、成本高且耗时(至少一个月),极大地阻碍了其实际应用.本研究介绍了一种基于微针的气动打印策略,可以实现高效无残留的患者来源类器官生物芯片构建.通过开发可打印的仿生水凝胶,肿瘤活检样本可以被高效地处理成生物墨水,培养过程中细胞存活率高达92％.使用微针进行打印,生物墨水利用率超过90％,可以高效地构建类器官生物芯片并用于药物测试,在一周内给出个性化的药物筛选信息.通过微打印策略和仿生水凝胶,细胞的利用率和类器官芯片的构建效率可以有效提高,为精准医学提供了新的途径.

Abstract

Organoid biochips can replicate the micro-en-vironment and functional traits of human organs in vitro,reflecting the physiological and pathological features of the human body.It provides a new platform for disease modeling and drug screening.However,the manual process of organoid cultivation and biochip construction using decellularized ex-tracellular matrix-based gel is typically complex,expensive,and time-consuming(at least one month),which significantly hinders practical application.Here,we introduce a micro-needle-based pneumatic printing strategy for residual-free and high-throughput construction of patient-derived orga-noid biochips.By developing printable and biomimetic hy-drogels,biopsy samples of cancer tissues can be effectively processed into discrete cells.Patient-derived colorectal cancer(CRC)cells in carboxymethylcellulose(CMC)and sodium al-ginate modified by adhesion sites exhibit high viability at 92％.Through a microneedle,the cell-ink utilization exceeds 90％.Especially,the organoid biochips can effectively be fabricated,and single cells in biochips can proliferate and differentiate into organoids with typical morphology.Finally,the patient-derived CRC organoids are used as the biochips for drug testing,which give the personalized drug screening informa-tion in a week.Overall,through the microprinting strategy and biomimetic hydrogels,the utilization rate of cells and the construction efficiency of organoid chips can be improved.This work provides a new approach for high-throughput printing patient-derived organoid biochips in precision med-icine.

关键词

bioprinting/biocompatible hydrogel/microneedle/organoid biochip/drug test

Key words

bioprinting/biocompatible hydrogel/microneedle/organoid biochip/drug test

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基金项目

National Key R&D Program of China(2023YFE0111500)

National Key R&D Program of China(2023YFC3040900)

National Natural Science Foundation of China(52222313)

National Natural Science Foundation of China(22075296)

National Natural Science Foundation of China(52321006)

National Natural Science Foundation of China(T2394480)

National Natural Science Foundation of China(T2394484)

National Natural Science Foundation of China(52203247)

China Postdoctoral Science Foundation(2022TQ0340)

Beijing National Laboratory for Molecular Sciences(BNLMS-CXXM-202005)

Junior Fellow Program of Beijing National Laboratory for Molecular Sciences(2021BMS20063)

出版年

2024

中国科学:材料科学(英文)

CSTPCD

ISSN：

段落导航