Development of a Hydrogel Platform with GBM and Microglia: A Potential Glioblastoma Tumor Model

Glioblastoma (GBM) is an aggressive brain tumor with a complex microenvironment shaped by a dense extracellular matrix (ECM) and dynamic interactions with stromal cells, presenting major challenges for in vitro modeling. In this study, we developed a biomimetic hydrogel platform by integrating a brain-derived decellularized extracellular matrix (dECM) with hyaluronic acid methacrylate (HAMA), yielding a composite (1H3D) that closely reflects the ECM characteristics of GBM tissue. Mechanically, 1H3D hydrogels exhibited a compressive modulus of 9.44 ± 0.73 kPa and an elastic modulus of 458.30 ± 13.39 Pa, resembling native GBM tissue. By retaining biochemical components from the brain dECM, hydrogels support key cellular processes such as adhesion, matrix remodeling, and invasion. These functions are essential for mimicking the highly invasive, plastic, and adaptive behavior of glioblastoma, thereby enhancing the physiological relevance of the in vitro platform. Coculture with microglia promoted glioblastoma progression, as evidenced by a 43% increase in K_i-67 expression and a 41% increase in invasion distance, underscoring the protumoral role of microglia–glioblastoma interactions within the engineered microenvironment. Altogether, integration of a GBM relevant hydrogel matrix with microglia coculture provides a biologically and mechanically representative in vitro platform that reproduces key features of tumor–stroma interactions, offering a useful tool for studying glioblastoma progression and enhancing the translational potential of preclinical models.