目前,在微组织工程中,越来越需要在细胞和组织的培养中模拟体内微环境。凹陷的微孔变得越来越受欢迎,因为与传统的微孔相比,它们可以提供更接近体内环境的微环境。这可以促进细胞和组织的培养。这里,我们将总结凹面微孔的制作方法,以及它们在微组织工程中的应用。凹面微孔的制作方法包括传统方法,如光刻和蚀刻,光刻胶的热回流,激光烧蚀,精密计算机数控(CNC)铣削,和新兴技术,如表面张力法,软膜的变形,3D打印,微珠的成型,气泡,和冷冻的水滴。凹形微孔的制造正在从专业的微制造实验室转移到普通的生化实验室,以促进其应用并为用户提供便利。凹面微孔主要用于芯片上器官模型,包括3D细胞聚集体的形成和培养(球体,类器官,和胚胎)。研究人员还使用微孔来研究底物拓扑结构对细胞行为的影响。我们将简要回顾它们在微组织工程的不同方面的应用,并讨论凹微孔的进一步应用。我们认为,通过不同细胞系的3D细胞聚集体构建多器官芯片将是凹面微孔的流行应用,而将生理相关分子分析与3D培养平台整合将是不久的将来的另一个流行应用。此外,来自这些生物系统的3D细胞聚集体将在药物筛选和异种植入中找到更多应用。
At present, there is an increasing need to mimic the in vivo micro-environment in the culture of cells and tissues in micro-tissue engineering. Concave microwells are becoming increasingly popular since they can provide a micro-environment that is closer to the in vivo environment compared to traditional microwells, which can facilitate the culture of cells and tissues. Here, we will summarize the fabrication methods of concave microwells, as well as their applications in micro-tissue engineering. The fabrication methods of concave microwells include traditional methods, such as lithography and etching, thermal reflow of photoresist, laser ablation, precision-computerized numerical control (CNC) milling, and emerging technologies, such as surface tension methods, the deformation of soft membranes, 3D printing, the molding of microbeads, air bubbles, and frozen droplets. The fabrication of concave microwells is transferring from professional microfabrication labs to common biochemical labs to facilitate their applications and provide convenience for users. Concave microwells have mostly been used in organ-on-a-chip models, including the formation and culture of 3D cell aggregates (spheroids, organoids, and embryoids). Researchers have also used microwells to study the influence of substrate topology on cellular behaviors. We will briefly
review their applications in different aspects of micro-tissue engineering and discuss the further applications of concave microwells. We believe that building multiorgan-on-a-chip by 3D cell aggregates of different cell lines will be a popular application of concave microwells, while integrating physiologically relevant molecular analyses with the 3D culture platform will be another popular application in the near future. Furthermore, 3D cell aggregates from these biosystems will find more applications in drug screening and xenogeneic implantation.