Macroporous chitosan/alginate hydrogels crosslinked with genipin accumulate and retain glioblastoma cancer cells

Abstract

Grade IV multiforme glioblastoma (GBM) is an aggressive cancer that remains incurable due to the GBM cells invading and proliferating in the surrounding healthy tissues, even after tumor resection. A new therapeutic paradigm to treat GBM is to attract and accumulate GBM cells in a macroporous hydrogel inserted in the surgical cavity after tumor resection, followed by a targeted high dose of radiotherapy. This work presents a molding-based method to prepare macroporous hydrogels composed of sodium alginate and chitosan, homogeneously mixed in solution using sodium bicarbonate, and subsequently crosslinked with genipin and calcium chloride. The gels display a blue color, the result of chitosan crosslinking with genipin, fully interconnected pores with an average diameter of 180 μm (and tunable over a wide range), with a compression modulus of 10 kPa, close to the value of brain tissues. The gels are stable in cell culture media and keep their integrity after radiation doses comparable to current GBM treatment levels. Finally, F98 GBM cells accumulate relatively homogeneously and are retained within the gels.