细胞、细胞外基质 (ECM) 和肿瘤微环境 (TME) 的空间异质性调节疾病进展和治疗效果。开发概括 TME 的体外模型有望加速肿瘤生物学研究并确定新的治疗靶点。在这里，我们使用基于挤出的多喷嘴 3D 生物打印，通过仿生 ECM 墨水对三阴性 MDA-MB-231 乳腺癌细胞、内皮细胞 (EC) 和人乳腺癌相关成纤维细胞 (HMCAF) 进行空间图案化。生物打印模型捕获了人类乳腺肿瘤空间结构的关键特征，包括不同大小的癌细胞密集区域和周围富含微血管的基质。血管生成和 ECM 硬化发生在基质区域，而不是富含癌细胞 (CCR) 的区域，类似于患者样本中的病理变化。转录组分析揭示了基质区域血管生成相关和 ECM 重塑相关特征的上调，并鉴定了这些过程的潜在配体受体 (LR) 介质。生物打印 TME 不同部位的乳腺癌细胞对化疗表现出不同的敏感性，凸显了环境介导的耐药性。总之，我们的 3D 生物打印肿瘤模型将作为一个平台来发现 TME 在癌症生物学和治疗中的综合功能。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Cellular, extracellular matrix (ECM), and spatial heterogeneity of tumor microenvironments (TMEs) regulate disease progression and treatment efficacy. Developing in vitro models that recapitulate the TME promises to accelerate studies of tumor biology and identify new targets for therapy. Here, we used extrusion-based, multi-nozzle 3D bioprinting to spatially pattern triple-negative MDA-MB-231 breast cancer cells, endothelial cells (ECs), and human mammary cancer-associated fibroblasts (HMCAFs) with biomimetic ECM inks. Bioprinted models captured key features of the spatial architecture of human breast tumors, including varying-sized dense regions of cancer cells and surrounding microvessel-rich stroma. Angiogenesis and ECM stiffening occurred in the stromal area but not the cancer cell-rich (CCR) regions, mimicking pathological changes in patient samples. Transcriptomic analyses revealed upregulation of angiogenesis-related and ECM remodeling-related signatures in the stroma region and identified potential ligand-receptor (LR) mediators of these processes. Breast cancer cells in distinct parts of the bioprinted TME showed differing sensitivities to chemotherapy, highlighting environmentally mediated drug resistance. In summary, our 3D-bioprinted tumor model will act as a platform to discover integrated functions of the TME in cancer biology and therapy.Copyright © 2024 Elsevier Ltd. All rights reserved.