Ort Carley, Chen Yimai, Ghagre Ajinkya, Ehrlicher Allen, Moraes Christopher
Department of Chemical Engineering, McGill University, 3610 rue University, Montreal H3A 0G4, Quebec, Canada.
Department of Bioengineering, McGill University, 817 Sherbrooke Street West, Montreal H3A 2K6, Quebec, Canada.
ACS Biomater Sci Eng. 2021 Jun 14;7(6):2814-2822. doi: 10.1021/acsbiomaterials.1c00129. Epub 2021 May 21.
3D culture platforms with tunable stiffness have the potential to improve many applications, such as drug discovery, organoid studies, and stem cell differentiation. Both dimensionality and stiffness regulate crucial and relevant cellular processes. However, 3D culture models are often limited in throughput and difficult to adopt for widespread use. Here, we demonstrate an accessible 3D, stiffness-tunable tissue culture platform, based on an interpenetrating network of collagen-1 and alginate. When blended with polymers that induce phase separation, these networks can be bioprinted at microliter volumes, using standard liquid handling infrastructure. We demonstrate robust reproducibility in printing these microgels, consistent tunability of mechanical properties, and maintained viability of multiple printed cell types. To highlight the utility and importance of this system, we demonstrate distinct morphological changes to cells in culture, use the system to probe the role of matrix mechanics and soluble factors in a collagen contraction assay, and perform a prototype viability screen against a candidate chemotherapeutic, demonstrating stiffness-dependent responses.
具有可调刚度的3D培养平台有潜力改善许多应用，如药物发现、类器官研究和干细胞分化。维度和刚度都调节关键且相关的细胞过程。然而，3D培养模型通常通量有限，难以广泛应用。在此，我们展示了一种基于胶原蛋白-1和藻酸盐互穿网络的、易于使用的3D、刚度可调的组织培养平台。当与诱导相分离的聚合物混合时，这些网络可以使用标准液体处理基础设施以微升体积进行生物打印。我们展示了打印这些微凝胶时的强大再现性、机械性能的一致可调性以及多种打印细胞类型的活力维持。为突出该系统的实用性和重要性，我们展示了培养细胞中明显的形态变化，使用该系统在胶原蛋白收缩试验中探究基质力学和可溶性因子的作用，并针对一种候选化疗药物进行了原型活力筛选，证明了刚度依赖性反应。
