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A major obstacle to effective treatment is the intricate tumor microenvironment (TME), which drives tumor progression and therapy resistance. However, existing in vitro models lack micrometer\u2010scale spatial control over multiple cellular components and fail to preserve their dynamic interactions, limiting our understanding of tumor biology and treatment responses. Here, we present a spatially controlled GBM\u2010on\u2010a\u2010chip (scGoC) platform that integrates a novel organoid positioning strategy, enabling the reconstruction of the TME within a 3D matrix at micron\u2010level precision. This platform allows real\u2010time monitoring of dynamic tumor\u2010immune\u2010vascular interactions, providing refined insights into tumor progression and drug responses. Using the scGoC, we demonstrate that endothelial cells not only promote microglial migration toward tumor organoids but also drive their polarization toward an immunosuppressive phenotype, faithfully recapitulating hallmark features of GBM progression. Importantly, the platform reveals a pro\u2010tumorigenic adaptive response to bevacizumab monotherapy, driven by the upregulation of HIF\u20101 signaling and metabolic reprogramming pathways, providing mechanistic insights into GBM treatment. Collectively, the scGoC establishes a versatile and standardized tool for decoding complex cellular communications and investigating mechanisms of treatment response with broad applicability across cancer research.<\/jats:p>","DOI":"10.1002\/adhm.71711","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:42:45Z","timestamp":1789022565000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Spatially Controlled Glioblastoma\u2010on\u2010a\u2010Chip for Dissecting Tumor\u2010Immune\u2010Vascular Crosstalk and Bevacizumab Resistance"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5889-2439","authenticated-orcid":false,"given":"Zixuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering Tsinghua University  Beijing China"},{"name":"Biomanufacturing and Engineering Living Systems Innovation International Talents Base  Beijing China"},{"name":"Beijing Key Laboratory of Intelligent Organ Biofabrication and Regenerative Repair  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4385-8373","authenticated-orcid":false,"given":"Jie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Tsinghua University  Beijing China"},{"name":"Biomanufacturing and Engineering Living Systems Innovation International Talents Base  Beijing China"},{"name":"Beijing Key Laboratory of Intelligent Organ Biofabrication and Regenerative Repair  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junned","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Tsinghua University  Beijing China"},{"name":"Biomanufacturing and Engineering Living Systems Innovation International Talents Base  Beijing China"},{"name":"Beijing Key Laboratory of Intelligent Organ Biofabrication and Regenerative Repair  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1582-9474","authenticated-orcid":false,"given":"Yongcong","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Tsinghua University  Beijing China"},{"name":"Biomanufacturing and Engineering Living Systems Innovation International Talents Base  Beijing China"},{"name":"Beijing Key Laboratory of Intelligent Organ Biofabrication and Regenerative Repair  Beijing China"},{"name":"State Key Laboratory of Tribology in Advanced Equipment Tsinghua University  Beijing China"},{"name":"State Key Laboratory of Clean and Efficient Turbomachinery Power Equipment, Department of Mechanical Engineering Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8507-9069","authenticated-orcid":false,"given":"Yanmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of New Materials and Advanced Manufacturing Beijing Academy of Science and Technology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Tsinghua University  Beijing China"},{"name":"Biomanufacturing and Engineering Living Systems Innovation International Talents Base  Beijing China"},{"name":"Beijing Key Laboratory of Intelligent Organ Biofabrication and Regenerative Repair  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Tsinghua University  Beijing China"},{"name":"Biomanufacturing and Engineering Living Systems Innovation International Talents Base  Beijing China"},{"name":"Beijing Key Laboratory of Intelligent Organ Biofabrication and Regenerative Repair  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7799-9210","authenticated-orcid":false,"given":"Heyun","family":"Mao","sequence":"additional","affiliation":[{"name":"TissHUe (Ningbo) Biomanufacturing Technology Co., Ltd.  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