Hydrogel matrix presence and composition influence drug responses of encapsulated glioblastoma spheroids

摘要: Abstract Glioblastoma multiforme (GBM) is the most aggressive brain tumor with median patient survival of 12-15 months. To facilitate treatment development, bioengineered GBM models that adequately recapitulate in vivo microenvironment are needed. Matrix-encapsulated multicellular spheroids represent such model because they solid characteristics, as dimensionality, cell-cell, and cell-matrix interactions. Yet, there no consensus to which matrix properties key improving predictive capacity spheroid-based drug screening platforms. We used a hydrogel-encapsulated spheroid model, where were independently altered investigate their effect on characteristics responsiveness. focused hydrogel degradability, tuned via enzymatically degradable crosslinkers, adhesiveness, integrin ligands. observed increased cellular infiltration resistance temozolomide degradable, adhesive hydrogels compared non-degradable, non-adhesive or free-floating spheroids. Further, higher index was noted for hydrogels. For hydrogels, we determined infiltrating cells more susceptible core. The susceptibility independent adhesion. could not attribute differential responses proliferation limited penetration into matrix. Our results suggest interactions guide responsiveness further elucidation these enable engineering