Patient-derived
glioblastoma organoid (GBO) growth in
hydrogels recapitulates key features of parental
tumors, making GBOs a useful tool for fundamental research on
cancer biology and offer deeper insight into the development of innovative therapeutic strategies for
cancer treatment.
Matrigel as a natural
hydrogel has been widely used for 3D culture in most
tumor organoid studies, but the volatility in its biochemical and biophysical properties makes it difficult to be further applied in GBO cultures. Thus, several kinds of biomimetic
hydrogels from synthetic or biological
polymers have been developed for
tumor organoid growth. Here, we innovatively utilize a photocurable
hydrogel-based biomimetic instructive system containing
gelatin methacryloyl (GelMA) mixed with a
hyaluronic acid (HA)
hydrogel as a scaffold for generating GBOs. Furthermore, we evaluated the GBO biological properties at the transcriptome level, which showed that GBOs cultured with this
hydrogel retain the expression profile of key neurodevelopmental markers, driving mutations and alternative splicing of parental
tumors. Notably, GBOs cultured with the photocurable
hydrogel may provide a platform for precision
cancer medicine, bridging the gap between basic research and clinical application. Although significant challenges remain, biomimetic
hydrogels can provide an exceptional window for the construction of
tumor organoids to ensure the accuracy of the research and clinical data.