Zhang Xiuxiu, Wang Zixian, Liu Zeyang, Zhan Zhen, Chen Jianwei, Xu Tao
Precision Medicine and Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen 518055, People's Republic of China.
Center for Bio-intelligent Manufacturing and Living Matter Bioprinting, Research Institute of Tsinghua University in Shenzhen, Tsinghua University, Shenzhen 518057, People's Republic of China.
Biofabrication. 2025 Jul 16;17(3). doi: 10.1088/1758-5090/adebb5.
The 3D hydrogel-based tumor model demonstrates significant potential in replicating the physiological characteristics oftumor environments for mechanistic studies and drug testing. However, the challenge persists in accurately mimicking a vascularized microtumor with a compartmentalized structure in a controlled, heterogeneous, and high-throughput manner. This study introduces a vascularized 3D tumor model that incorporates an endothelial cell (EC) barrier, created by encapsulating glioma cells and human umbilical vein endothelial cells (HUVECs) within the core (6% gelatin) and shell (10% GelMa) of core-shell microbeads, respectively. Upon culture, the tumor cells develop spheroids within the liquid core, while the HUVECs in the shell migrate and adhere to the GelMa surface, ultimately forming an EC barrier. This 3D microengineered tumor model exhibits angiogenesis in solid tumor spheroids, effectively mirroring thestructure and providing relevant biochemical and biophysical properties. Notably, in comparison to 2D cell cultures, the vascularized tumor model shows significantly higher half-maximal inhibitory concentrations for the anticancer drug doxorubicin. Collectively, these findings highlight the considerable potential of engineered 3D tumor models in drug testing.
基于3D水凝胶的肿瘤模型在复制肿瘤环境的生理特征以进行机制研究和药物测试方面显示出巨大潜力。然而,以可控、异质和高通量的方式准确模拟具有分隔结构的血管化微肿瘤仍然是一个挑战。本研究引入了一种血管化3D肿瘤模型,该模型包含一个内皮细胞(EC)屏障,通过将胶质瘤细胞和人脐静脉内皮细胞(HUVECs)分别封装在核壳微珠的核心(6%明胶)和壳层(10% GelMa)中创建。培养后,肿瘤细胞在液体核心内形成球体,而壳层中的HUVECs迁移并粘附在GelMa表面,最终形成一个EC屏障。这种3D微工程肿瘤模型在实体肿瘤球体中表现出血管生成,有效地反映了其结构并提供了相关的生化和生物物理特性。值得注意的是,与二维细胞培养相比,血管化肿瘤模型对抗癌药物阿霉素的半数最大抑制浓度显著更高。总的来说,这些发现突出了工程化3D肿瘤模型在药物测试中的巨大潜力。