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体外肿瘤模型的生物打印用于个性化癌症治疗:综述。

Bioprinting of in vitro tumor models for personalized cancer treatment: a review.

机构信息

Department of Mechanical Engineering, Biomanufacturing Center, Tsinghua University, Beijing, People's Republic of China. Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, People's Republic of China. 'Biomanufacturing and Engineering Living Systems' 111 -Innovation International Talents Base, Beijing, People's Republic of China.

出版信息

Biofabrication. 2020 Jul 9;12(4):042001. doi: 10.1088/1758-5090/ab97c0.

Abstract

Studying biological characteristics of tumors and evaluating the treatment effects require appropriate in vitro tumor models. However, the occurrence, progression, and migration of tumors involve spatiotemporal changes, cell-microenvironment and cell-cell interactions, and signal transmission in cells, which makes the construction of in vitro tumor models extremely challenging. In the past few years, advances in biomaterials and tissue engineering methods, especially development of the bioprinting technology, have paved the way for innovative platform technologies for in vitro cancer research. Bioprinting can accurately control the distribution of cells, active molecules, and biomaterials. Furthermore, this technology recapitulates the key characteristics of the tumor microenvironment and constructs in vitro tumor models with bionic structures and physiological systems. These models can be used as robust platforms to study tumor initiation, interaction with the microenvironment, angiogenesis, motility and invasion, as well as intra- and extravasation. Bioprinted tumor models can also be used for high-throughput drug screening and validation and provide the possibility for personalized cancer treatment research. This review describes the basic characteristics of the tumor and its microenvironment and focuses on the importance and relevance of bioprinting technology in the construction of tumor models. Research progress in the bioprinting of monocellular, multicellular, and personalized tumor models is discussed, and comprehensive application of bioprinting in preclinical drug screening and innovative therapy is reviewed. Finally, we offer our perspective on the shortcomings of the existing models and explore new technologies to outline the direction of future development and application prospects of next-generation tumor models.

摘要

研究肿瘤的生物学特性和评估治疗效果需要合适的体外肿瘤模型。然而,肿瘤的发生、发展和迁移涉及时空变化、细胞-微环境和细胞-细胞相互作用以及细胞内信号转导,这使得体外肿瘤模型的构建极具挑战性。在过去的几年中,生物材料和组织工程方法的进步,特别是生物打印技术的发展,为体外癌症研究的创新平台技术铺平了道路。生物打印可以精确控制细胞、活性分子和生物材料的分布。此外,该技术再现了肿瘤微环境的关键特征,并构建了具有仿生结构和生理系统的体外肿瘤模型。这些模型可用作研究肿瘤起始、与微环境相互作用、血管生成、运动和侵袭以及细胞内和细胞外转移的强大平台。生物打印的肿瘤模型还可用于高通量药物筛选和验证,并为个性化癌症治疗研究提供可能性。本文描述了肿瘤及其微环境的基本特征,重点介绍了生物打印技术在肿瘤模型构建中的重要性和相关性。讨论了单细胞、多细胞和个性化肿瘤模型的生物打印研究进展,并综述了生物打印在临床前药物筛选和创新治疗中的综合应用。最后,我们提出了对现有模型的不足的看法,并探讨了新技术,以勾勒出下一代肿瘤模型的未来发展方向和应用前景。

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