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@ARTICLE{Trautmann:283218,
      author       = {Trautmann, Rajvinder Kaur and Dennison, Nicholas and
                      McCortney, Kathleen and Klier, Solveig and Cosacak, Mehmet
                      Ilyas and Werner, Carsten and Akyoldas, Goktug and
                      Horbinski, Craig M. and Freudenberg, Uwe and Kizil, Caghan},
      title        = {{H}igh‐{T}hroughput 3{D} {G}lioblastoma {M}odel in
                      {G}lycosaminoglycan {H}ydrogels for {P}ersonalized
                      {T}herapeutic {S}creening},
      journal      = {Macromolecular bioscience},
      volume       = {26},
      number       = {1},
      issn         = {1616-5187},
      address      = {Weinheim},
      publisher    = {Wiley-VCH},
      reportid     = {DZNE-2026-00067},
      pages        = {e00394},
      year         = {2026},
      abstract     = {Glioblastoma (GBM) is a devastating brain tumor with
                      limited treatment success, partly because in vitro models
                      poorly mimic in vivo complexity. This study introduces a
                      high-throughput 3D culture platform utilizing modular
                      starPEG–glycosaminoglycan (GAG) hydrogels that enable
                      independent control of extracellular matrix (ECM) cues:
                      stiffness, cytokine affinity, matrix
                      metalloproteinase-responsive remodeling, and cell
                      adhesiveness via integrin-binding RGD peptides. This
                      platform supports encapsulation of patient-derived GBM
                      cells, recreates physiologically relevant tumor
                      microenvironments in 384-well plates, and enables automated
                      drug testing on primary cells. Transcriptomic analyses show
                      that 3D cultures recapitulate primary and recurrent GBM
                      programs- including hypoxia-, immune-, and ECM-regulatory
                      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-dependent reductions in invasive filaments and spheroid
                      architecture with 5-fluorouracil/uridine and carmustine,
                      demonstrating its potential for optimizing combinatorial
                      therapies. This 3D model surpasses 2D cultures, capturing
                      tumor-specific 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-cultures.
                      By delivering reliable, individualized therapeutic data
                      within a short timeframe, this model holds transformative
                      potential for personalized GBM treatment.},
      cin          = {AG Kizil},
      ddc          = {570},
      cid          = {I:(DE-2719)1710007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1002/mabi.202500394},
      url          = {https://pub.dzne.de/record/283218},
}