Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.
The State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
Lab Chip. 2021 Apr 20;21(8):1604-1612. doi: 10.1039/d1lc00003a.
The fabrication of functional tissue is important for tissue engineering, regenerative medicine, and biological research. However, current 3D bioprinting technologies mean it is hard to precisely arrange bioinks (composed of cells and materials) in a high-fidelity 3D structure and print cells of multiple types with sufficient concentrations and superior viabilities; this can severely constrain cell growth, interactions, and functions. Here, an acoustic droplet printing method is introduced to solve these problems in 3D bioprinting. Being nozzle-free, the acoustic printer stably enables high-concentration cells, or even cell spheroids, to be printed without clogging. Cell viability (>94%) using post acoustic printing is higher than those obtained with currently used inkjet-based (>85%) and extrusion-based (40-80%) bioprinting methods. Also, this method involves a small printer that can be flexibly integrated, allowing different kinds of bioinks to be printed. Moreover, the limited printability of low-concentration gelatin methacryloyl (5% (w/v) GelMA) materials is overcome by determining the positioning, fluidity (e.g., spreading), and 3D morphology of the GelMA droplets; therefore, high-fidelity 3D constructs can be fabricated. As a proof of concept, a tumor microenvironment consisting of one tumor spheroid surrounded by a high concentration of cancer-associated fibroblasts (CAFs) was constructed; this was able to establish a dynamic tumor invasion function modulated by reciprocal tumor cell-CAF interactions. The nozzle-free, contact-free, and low cell-damage merits of this method will advance bioprinting, allowing the creation of more functional native tissues, organoids, or disease models.
功能组织的制造对于组织工程、再生医学和生物研究非常重要。然而，目前的 3D 生物打印技术难以精确地将生物墨水（由细胞和材料组成）排列在高保真 3D 结构中，并且难以以足够的浓度和优异的活力打印多种类型的细胞；这可能严重限制细胞的生长、相互作用和功能。在这里，引入了一种声滴打印方法来解决 3D 生物打印中的这些问题。由于无喷嘴，声打印机能够稳定地打印高浓度的细胞，甚至细胞球体，而不会堵塞。与目前使用的喷墨（>85%）和挤出（40-80%）生物打印方法相比，声打印后的细胞活力（>94%）更高。此外，该方法涉及一种小型打印机，可以灵活集成，允许打印不同种类的生物墨水。而且，通过确定 5%（w/v）明胶甲基丙烯酰（GelMA）材料的定位、流动性（例如，铺展）和 3D 形态，可以克服低浓度 GelMA 材料的有限可打印性；因此，可以制造出高保真 3D 结构。作为概念验证，构建了一个由一个肿瘤球体周围环绕高浓度癌相关成纤维细胞（CAFs）组成的肿瘤微环境；这能够建立由肿瘤细胞-CAF 相互作用调节的动态肿瘤侵袭功能。该方法无喷嘴、无接触且对细胞损伤小，将推进生物打印技术，使更多具有功能的天然组织、类器官或疾病模型得以创建。
