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This study introduces a high\u2010throughput 3D culture platform utilizing modular starPEG\u2013glycosaminoglycan (GAG) hydrogels that enable independent control of extracellular matrix (ECM) cues: stiffness, cytokine affinity, matrix metalloproteinase\u2010responsive remodeling, and cell adhesiveness via integrin\u2010binding RGD peptides. This platform supports encapsulation of patient\u2010derived GBM cells, recreates physiologically relevant tumor microenvironments in 384\u2010well plates, and enables automated drug testing on primary cells. Transcriptomic analyses show that 3D cultures recapitulate primary and recurrent GBM programs\u2010 including hypoxia\u2010, immune\u2010, and ECM\u2010regulatory pathways driving growth, invasion, and resistance, without externally imposed hypoxia. The platform's versatility extends to drug screening, where single and combinatorial treatments produce reproducible cytoskeletal and transcriptomic responses. Notably, the system revealed dose\u2010dependent reductions in invasive filaments and spheroid architecture with 5\u2010fluorouracil\/uridine and carmustine, demonstrating its potential for optimizing combinatorial therapies. This 3D model surpasses 2D cultures, capturing tumor\u2010specific molecular programs and offering a robust tool for translational research. Despite lacking vascular or immune components, its tunability, scalability, and clinical relevance make it a strong basis for advanced co\u2010cultures. By delivering reliable, individualized therapeutic data within a short timeframe, this model holds transformative potential for personalized GBM treatment.\n                  <\/jats:p>","DOI":"10.1002\/mabi.202500394","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:26:16Z","timestamp":1768461976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High\u2010Throughput 3D Glioblastoma Model in Glycosaminoglycan Hydrogels for Personalized Therapeutic Screening"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9417-3716","authenticated-orcid":false,"given":"Rajvinder Kaur","family":"Trautmann","sequence":"first","affiliation":[{"name":"Neuron\u2010D GmbH  Dresden Germany"},{"name":"Leibniz Institute of Polymer Research Dresden (IPF)  Dresden 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