High‑Throughput 3D Glioblastoma Model in Glycosaminoglycan Hydrogels for Personalized Therapeutic Screening
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.
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.
The platform enables scalable, patient‑specific therapeutic screening in a chemically defined 3D microenvironment that better mimics GBM biology and allows rapid assessment of drug efficacy, supporting personalized medicine.
Evidence level: Feltételezés / hírjelzés. Nincs önálló tudományos bizonyíték.
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