Abstract：
The evaluation of anti-tumor drugs is critical for their development and clinical guidance. Tumor organoid models are gaining increased attention due to their ability to better mimic real tumor tissues, as well as lower time and economic costs, which makes up for the shortcomings of cell lines and xenograft models. However, current tumor organoid cultures based on the Matrigel have limitations in matching with high-throughput engineering methods due to slow gelation and low mechanical strength. Here, we present a novel composite bioink for culturing colorectal cancer organoids that provides an environment close to real tissue growth conditions and exhibits excellent photocrosslinking properties for rapid gel formation. Most importantly, the tumor organoids viability in the composite bioink after printing was as high as 97%, which also kept multicellular polar structures consistent with traditional culture methods in the Matrigel. Using 3D bioprinting with this composite bioink loaded with organoids, we demonstrated the feasibility of this drug evaluation model by validating it with clinically used colorectal cancer treatment drugs. Our results suggested that the composite bioink could effectively cultivate tumor organoids using 3D bioprinting, which had the potential to replace less reliable manual operations in promoting the application of tumor organoids in drug development and clinical guidance.
摘要：
抗肿瘤药物的评价对其开发和临床指导至关重要。肿瘤类器官模型由于其更好地模拟真实肿瘤组织的能力而获得越来越多的关注。以及更低的时间和经济成本，弥补了细胞系和异种移植模型的不足。然而,目前基于Matrigel的肿瘤类器官培养物由于缓慢的凝胶化和低的机械强度而在与高通量工程方法匹配方面具有局限性。这里,我们提出了一种用于培养结直肠癌类器官的新型复合生物墨水，该生物墨水提供了接近真实组织生长条件的环境，并表现出优异的光交联特性，可快速形成凝胶。最重要的是,打印后复合生物墨水中的肿瘤类器官活力高达97%，这也保持了多细胞极性结构与Matrigel中的传统培养方法一致。使用这种载有类器官的复合生物墨水进行3D生物打印，我们通过与临床使用的结直肠癌治疗药物进行验证,证明了该药物评价模型的可行性.我们的结果表明，复合生物墨水可以使用3D生物打印有效培养肿瘤类器官，有可能取代不太可靠的手工操作，以促进肿瘤类器官在药物开发和临床指导中的应用。
