Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
Ann Biomed Eng. 2020 Jul;48(7):2002-2027. doi: 10.1007/s10439-020-02498-w. Epub 2020 Apr 13.
The development of novel 3D tissue culture systems has enabled the in vitro study of in vivo processes, thereby overcoming many of the limitations of previous 2D tissue culture systems. Advances in biomaterials, including the discovery of novel synthetic polymers has allowed for the generation of physiologically relevant in vitro 3D culture models. A large number of 3D culture systems, aided by novel organ-on-a-chip and bioreactor technologies have been developed to improve reproducibility and scalability of in vitro organ models. The discovery of induced pluripotent stem cells (iPSCs) and the increasing number of protocols to generate iPSC-derived cell types has allowed for the generation of novel 3D models with minimal ethical limitations. The production of iPSC-derived 3D cultures has revolutionized the field of developmental biology and in particular, the study of fetal brain development. Furthermore, physiologically relevant 3D cultures generated from PSCs or adult stem cells (ASCs) have greatly advanced in vitro disease modelling and drug discovery. This review focuses on advances in 3D culture systems over the past years to model fetal development, disease pathology and support drug discovery in vitro, with a specific focus on the enabling role of biomaterials.
新型 3D 组织培养系统的发展使人们能够在体外研究体内过程，从而克服了先前 2D 组织培养系统的许多局限性。生物材料的进步，包括新型合成聚合物的发现，使得能够生成生理相关的体外 3D 培养模型。大量的 3D 培养系统，借助新型器官芯片和生物反应器技术得以开发，以提高体外器官模型的可重复性和可扩展性。诱导多能干细胞（iPSCs）的发现以及越来越多的生成 iPSC 衍生细胞类型的方案，使得可以生成具有最小伦理限制的新型 3D 模型。iPSC 衍生的 3D 培养物的产生彻底改变了发育生物学领域，特别是胎儿大脑发育的研究。此外，源自 PSCs 或成体干细胞（ASCs）的生理相关 3D 培养物极大地促进了体外疾病建模和药物发现。本综述重点介绍了过去几年中用于模拟胎儿发育、疾病病理学和支持体外药物发现的 3D 培养系统的进展，特别强调了生物材料的使能作用。
