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.

中文翻译：

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基于微流体的细胞负载微凝胶的制造


微流体原理已被广泛用作强大的工具来制造受控的单分散的充满细胞的水凝胶微滴，用于各种生物应用，特别是组织工程。在这篇综述中，我们报告了基于微流体的液滴制造的最新进展，并提供了我们的理由来证明基于微流体的技术在实现水凝胶内细胞封装方面相对于其他微技术方法的优越性。该系统的三个主要组成部分——水凝胶、细胞和设备配置——都经过彻底检查。首先，研究了各种类型水凝胶的特性，包括天然和合成类型，特别是在细胞封装方面。接下来阐明选择特定细胞进行封装的原因。接下来，除了详细讨论各自的液滴形成机制外，还对有助于实现细胞封装的各种装置配置（包括 T 形接头、流动聚焦和共流）进行了批判性回顾。然后，我们展望了当前载有细胞的水凝胶液滴在组织工程中的应用，例如 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-微环境相互作用的平台的用途。最后，我们阐明了基于微流体技术生产载有细胞的微凝胶的前景，并为未来的研究提出了一些方向，这些方向可以帮助克服目前阻碍该技术转化为临床成功的挑战。