原发性癌症调节骨骼微环境，在肿瘤细胞中播种休眠并发生转移，导致多器官转移和死亡。本研究结合三维打印和骨芯片（BOC）技术，开发出一种模拟前转移微环境（PMNs）的BOC平台，有助于阐明原发性癌症影响下骨内细胞与转移性肿瘤细胞之间的相互作用。使用可光交联明胶甲基丙烯酸酯（GelMA）作为三维培养水凝胶，包埋细胞，并将循环的肿瘤培养基（CM）与水凝胶相邻以验证间充质干细胞（MSCs）和破骨细胞（RAW264.7s）的关键作用。设计了三个微环境：休眠微环境、周血管微环境和“恶性循环”微环境，以在一个芯片上重现骨转移，并实现高细胞存活率和良好养分交换。就肿瘤休眠与再激活而言，研究了A549肺癌细胞通过cortactin通路与MSCs和RAW264.7之间的侵袭足突形成。作为概念验证，通过分析侵袭足突形成和各种细胞的影响，证明了平台的功能和实用性，并为了解PMN形成和相关药物研发铺平了道路。© 2023 Wiley-VCH GmbH.

Primary cancer modulates the bone microenvironment to sow the seeds of dormancy and metastasis in tumor cells, leading to multiple organ metastasis and death. In this study, 3D printing and bone-on-a-chip (BOC) are combined to develop a BOC platform that mimics the pre-metastatic niches (PMNs) and facilitates elucidation of the interactions between bone-resident cells and metastatic tumor cells under the influence of primary cancer. Photocrosslinkable gelatin methacrylate (GelMA) is used as a 3D culturing hydrogel to encapsulate cells, and circulate tumor culture medium (CM) adjacent to the hydrogel to verify the critical role of mesenchymal stem cells (MSCs) and osteoclasts (RAW264.7s). Three niches: the dormancy niche, the perivascular niche, and the "vicious cycle" niche, are devised to recapitulate bone metastasis in one chip with high cell viability and excellent nutrient exchange. With respect to tumor dormancy and reactivation, the invadopodia formation of A549 lung cancer cells in communication with MSCs and RAW264.7 via the cortactin pathway is researched. As a proof of concept, the functionality and practicality of the platform are demonstrated by analyzing the invadopodia formation and the influence of various cells, and the establishment of the dynamic niches paves the way to understanding PMN formation and related drug discovery.© 2023 Wiley-VCH GmbH.