Division of Chemical Engineering, Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka, Osaka, Japan.
Lab Chip. 2024 Sep 24;24(19):4571-4580. doi: 10.1039/d4lc00552j.
Recently, the 3D printing of cell-laden hydrogel structures, known as bioprinting, has received increasing attention owing to advances in tissue engineering and drug screening. However, a micromixing technology that efficiently mixes viscous bioinks under mild conditions is needed. Therefore, this study presents a novel method for achieving homogeneous mixing of multiple inks in 3D bioprinting through acoustic stimulation. This technique involves generating an acoustic microstream through bubble oscillations inside a 3D bioprinting nozzle. We determined the optimal hole design for trapping a bubble, hole arrangement, and voltage for efficient mixing, resulting in a four-fold increase in mixing efficiency compared to a single bubble arrangement. Subsequently, we propose a nozzle design for efficient mixing during bioprinting. The proposed nozzle design enabled the successful printing of line structures with a uniform mixture of different viscous bioinks, achieving a mixing efficiency of over 80% for mixing 0.5-1.0 wt% sodium alginate aqueous solutions. Additionally, acoustic stimulation had no adverse effects on cell viability, maintaining a high cell viability of 88% after extrusion. This study presents the first use of a bubble micromixer in 3D bioprinting, demonstrating gentle yet effective multi-ink mixing. We believe this approach will broaden 3D printing applications, particularly for constructing functional structures in 3D bioprinting.
最近，由于组织工程和药物筛选方面的进展，细胞负载水凝胶结构的 3D 打印（即生物打印）受到了越来越多的关注。然而，需要一种能够在温和条件下有效混合粘性生物墨水的微混合技术。因此，本研究提出了一种通过声刺激实现 3D 生物打印中多种墨水均匀混合的新方法。该技术涉及通过在 3D 生物打印喷嘴内的气泡振荡产生声微流。我们确定了用于捕获气泡的最佳孔设计、孔排列和电压，从而使混合效率比单个气泡排列提高了四倍。随后，我们提出了一种用于生物打印中有效混合的喷嘴设计。所提出的喷嘴设计能够成功打印出不同粘性生物墨水均匀混合的线条结构，对于混合 0.5-1.0wt%的海藻酸钠水溶液，混合效率超过 80%。此外，声刺激对细胞活力没有不良影响，挤出后细胞活力保持在 88%的高水平。本研究首次在 3D 生物打印中使用气泡微混合器，展示了温和而有效的多墨水混合方法。我们相信这种方法将拓宽 3D 打印的应用范围，特别是在构建 3D 生物打印中的功能性结构方面。
