Department of Micro-Nano Systems Engineering, Graduate School of Engineering, Nagoya University, Nagoya, 464-8603, Japan.
Biomed Microdevices. 2012 Dec;14(6):1085-93. doi: 10.1007/s10544-012-9713-0.
Techniques that allow cells to self-assemble into three-dimensional (3D) spheroid microtissues provide powerful in vitro models that are becoming increasingly popular in fields such as stem cell research, tissue engineering, and cancer biology. Appropriate simulation of the 3D environment in which tissues normally develop and function is crucial for the engineering of in vitro models that can be used for the formation of complex tissues. We have developed a unique multicellular aggregate formation platform that utilizes a maskless gray-scale photolithography. The cellular aggregate formed using this platform has a toroidal-like geometry and includes a micro lumen that facilitates the supply of oxygen and growth factors and the expulsion of waste products. As a result, this platform was capable of rapidly producing hundreds of multicellular aggregates at a time, and of regulating the diameter of aggregates with complex design. These toroidal multicellular aggregates can grow as long-term culture. In addition, the micro lumen can be used as a continuous channel and for the insertion of a vascular system or a nerve system into the assembled tissue. These platform characteristics highlight its potential to be used in a wide variety of applications, e.g. as a bioactuator, as a micro-machine component or in drug screening and tissue engineering.
能够使细胞自我组装成三维（3D）球体微组织的技术为体外模型提供了强大的支持，这些模型在干细胞研究、组织工程和癌症生物学等领域越来越受欢迎。适当模拟组织正常发育和功能的 3D 环境对于工程体外模型至关重要，这些模型可用于复杂组织的形成。我们开发了一种独特的利用无掩模灰度光刻技术的多细胞聚集体形成平台。使用该平台形成的细胞聚集体具有环形几何形状，并包含一个微腔，有利于氧气和生长因子的供应以及废物的排出。因此，该平台能够一次快速生成数百个多细胞聚集体，并能够用复杂设计来调节聚集体的直径。这些环形多细胞聚集体可以作为长期培养物进行生长。此外，微腔可用作连续通道，并可将血管系统或神经系统插入组装好的组织中。这些平台特性突出了其在广泛应用中的潜力，例如作为生物执行器、微机器组件或在药物筛选和组织工程中的应用。
