癌症治疗抵抗是由肿瘤内存在各种类型的细胞和异质性引起的。肿瘤细胞与细胞-微环境的相互作用在肿瘤的进展和侵袭中起着重要作用，这对于诊断和耐药化疗有重要意义。在本研究中，我们开发了3D生物印刷的体外模型，模拟了由共培养细胞在具有控制结构的水凝胶基质中分布的乳腺癌肿瘤微环境的模型。我们假设肿瘤可以通过癌细胞负载的共培养水凝胶构造来表示，而其微环境可以在能产生化学梯度的微流控芯片中进行建模。乳腺癌细胞（MCF7和MDA-MB-231）和非肿瘤性乳腺上皮细胞（MCF10A）被嵌入藻酸盐-明胶水凝胶中，并使用多头挤出生物印刷机进行印刷。我们的方法能够对共培养系统中的细胞的位置和排列进行精确控制，使得能够设计各种肿瘤结构。我们创建了具有两种不同类型细胞的样本，这些细胞在特定的初始位置上被精确控制着每种细胞类型的密度。这些细胞要么是随机混合的，要么是按顺序分层放置以创建细胞异质性。为了研究细胞对化学诱导的迁移，我们在一间带有逐渐化学梯度的腔室中开发了一个化学微环境。作为一个概念验证，我们使用这个装置研究了在不同比例的MCF10A细胞存在下，MDA-MB-231细胞对上皮生长因子梯度的不同迁移模式。我们的方法结合了3D生物印刷和微流体设备，可以创建多样的肿瘤结构，这些结构代表了不同患者中的肿瘤。这提供了一个优秀的工具，用于以高空间和时间分辨率研究癌细胞的行为。© 2023 Springer Nature Limited.

Cancer treatment resistance is a caused by presence of various types of cells and heterogeneity within the tumor. Tumor cell-cell and cell-microenvironment interactions play a significant role in the tumor progression and invasion, which have important implications for diagnosis, and resistance to chemotherapy. In this study, we develop 3D bioprinted in vitro models of the breast cancer tumor microenvironment made of co-cultured cells distributed in a hydrogel matrix with controlled architecture to model tumor heterogeneity. We hypothesize that the tumor could be represented by a cancer cell-laden co-culture hydrogel construct, whereas its microenvironment can be modeled in a microfluidic chip capable of producing a chemical gradient. Breast cancer cells (MCF7 and MDA-MB-231) and non-tumorigenic mammary epithelial cells (MCF10A) were embedded in the alginate-gelatine hydrogels and printed using a multi-cartridge extrusion bioprinter. Our approach allows for precise control over position and arrangements of cells in a co-culture system, enabling the design of various tumor architectures. We created samples with two different types of cells at specific initial locations, where the density of each cell type was carefully controlled. The cells were either randomly mixed or positioned in sequential layers to create cellular heterogeneity. To study cell migration toward chemoattractant, we developed a chemical microenvironment in a chamber with a gradual chemical gradient. As a proof of concept, we studied different migration patterns of MDA-MB-231 cells toward the epithelial growth factor gradient in presence of MCF10A cells in different ratios using this device. Our approach involves the integration of 3D bioprinting and microfluidic devices to create diverse tumor architectures that are representative of those found in various patients. This provides an excellent tool for studying the behavior of cancer cells with high spatial and temporal resolution.© 2023. Springer Nature Limited.