肿瘤微环境（TME）是一个复杂的系统，包括多个成分，其中血管在通过血管内皮屏障为肿瘤组织提供营养、氧气和生长因子，同时还可以通过血管内皮屏障向肿瘤组织输送化疗药物。为了在体外复制TME，已经开发出了几种生物打印和微流体芯片技术。然而，这些技术在生物打印和微流体学的潜在益处方面还没有得到充分利用，如对生物样本的精确空间控制、在一个微流体设备中构建多个TME和改变培养环境以获得更好的生物相似性的能力。此外，在将模型应用于药物治疗和筛选之前，还应考虑到TME模型中血管内皮屏障和肿瘤组织的复杂运输现象。在本研究中，我们描述了一种新的综合技术，通过在微流控芯片上打印一个自组织的TME阵列，该芯片由环绕乳腺癌球体的血管内皮屏障组成，解决了这些问题。为了将TME阵列整合到微流控平台上，我们开发了一种用于挤出生物打印的微流摄基板，用于细胞培养平台，可以通过微结构控制扩散性，并在培养通道内建立灌注培养环境。我们还分析了TME阵列内的细胞行为，以研究扩散性对形成乳腺癌球体周围血管内皮屏障的自组织过程的影响。

A tumor microenvironment (TME) is a complex system that comprises various components, including blood vessels that play a crucial role in supplying nutrients, oxygen, and growth factors, as well as delivering chemotherapy drugs to the tumor mass through the vascular endothelial barrier. To replicate the TME in vitro, several bioprinting and microfluidic organ-on-a-chip technologies have been developed. However, these technologies have not been fully exploited in terms of potential benefits of bioprinting and microfluidics, such as precise spatial control for biological samples, construction of multiple TMEs per microfluidic device, and the ability to adjust culture environments for better biological similarity. In addition, the complex transport phenomena within the vascular endothelial barrier and the aggregated tumor mass in the TME model should be considered before applying the model to drug treatment and screening. In this study, we describe a novel integrative technology that addresses these issues by introducing a self-organized TME array bioprinted on a microfluidic chip consisting of a vascular endothelial barrier surrounding breast cancer spheroids. To integrate the TME array onto the microfluidic platform, a microfluidic substrate for extrusion bioprinting was developed for a cell culture platform, which enables diffusivity control by microstructures and establishes a perfusion culture environment inside the culture channel. We also analyzed the cellular behaviors within the TME array to investigate the influence of the diffusivity on the self-organization process required to form the vascular endothelial barrier surrounding breast cancer spheroids.