Mohamed Mohamed G A, Ambhorkar Pranav, Samanipour Roya, Yang Annie, Ghafoor Ali, Kim Keekyoung
School of Engineering, University of British Columbia, Kelowna, British Columbia V1V 1V7, Canada.
Irving K. Barber School of Arts and Sciences, University of British Columbia, Kelowna, British Columbia V1V 1V7, Canada.
Biomicrofluidics. 2020 Mar 5;14(2):021501. doi: 10.1063/1.5134060. eCollection 2020 Mar.
Microfluidic principles have been extensively utilized as powerful tools to fabricate controlled monodisperse cell-laden hydrogel microdroplets for various biological applications, especially tissue engineering. In this review, we report recent advances in microfluidic-based droplet fabrication and provide our rationale to justify the superiority of microfluidics-based techniques over other microtechnology methods in achieving the encapsulation of cells within hydrogels. The three main components of such a system-hydrogels, cells, and device configurations-are examined thoroughly. First, the characteristics of various types of hydrogels including natural and synthetic types, especially concerning cell encapsulation, are examined. This is followed by the elucidation of the reasoning behind choosing specific cells for encapsulation. Next, in addition to a detailed discussion of their respective droplet formation mechanisms, various device configurations including T-junctions, flow-focusing, and co-flowing that aid in achieving cell encapsulation are critically reviewed. We then present an outlook on the current applications of cell-laden hydrogel droplets in tissue engineering such as 3D cell culturing, rapid generation and repair of tissues, and their usage as platforms for studying cell-cell and cell-microenvironment interactions. Finally, we shed some light upon the prospects of microfluidics-based production of cell-laden microgels and propose some directions for forthcoming research that can aid in overcoming challenges currently impeding the translation of the technology into clinical success.
微流控原理已被广泛用作强大的工具，用于制造用于各种生物应用（尤其是组织工程）的可控单分散载细胞水凝胶微滴。在本综述中，我们报告了基于微流控的微滴制造的最新进展，并阐述了我们的理由，以证明基于微流控的技术在实现细胞包封于水凝胶中方面优于其他微技术方法。对该系统的三个主要组成部分——水凝胶、细胞和设备配置——进行了全面研究。首先，研究了包括天然和合成类型在内的各种水凝胶的特性，特别是关于细胞包封方面。其次，阐明了选择特定细胞进行包封背后的推理。接下来，除了详细讨论它们各自的微滴形成机制外，还对有助于实现细胞包封的各种设备配置（包括T型接头、流动聚焦和共流）进行了严格审查。然后，我们展望了载细胞水凝胶微滴在组织工程中的当前应用，如3D细胞培养、组织的快速生成和修复，以及它们作为研究细胞-细胞和细胞-微环境相互作用平台的用途。最后，我们阐述了基于微流控生产载细胞微凝胶的前景，并为即将开展的研究提出了一些方向，这些研究有助于克服目前阻碍该技术转化为临床成功的挑战。
