SUPERSOFT SPONGE-LIKE CRYOGEL AS AN IMPLANT TO TREAT GLIOBLASTOMA

Abstract AIMS Create cylindrical cryogels with well-defined size. Investigate clemastine drug loading capicaty and drug release patterns. Investigate in vitro and in vivo safety and antitumor efficacy. METHOD A 3D printed template was designed and printed to make cylindrical shape cryogels. The morphology of cryogels was characterized by bright field photos, SEM, FTIR and confocal microscopy photos. The mechanical property was evaluated by uniaxial compression tests. The orthotropic glioblastoma tumor model was established by engrafting BT12 human glioblastoma stem cells intracerebrally into immunocompromised nude mice. The tumor was surgically removed after two weeks and the cryogel was implanted into the resection cavity. Animals were euthanized after two weeks, and their brains were collected for the immunohistochemistry. RESULTS Cylindrical cryogels were prepared to exactly fit the biopsy resection cavity in the mouse glioblastoma tumor resected model. The macropore structure in the cryogel was observed under confocal microscopy. Young’s modulus of the cryogel was only 1.6 kPa. The loading capacity of clemastine in one cryogel was more than 100 μg. Clemastine could be sustained released for around a week. In vitro cell viability studies showed that empty cryogels were not toxic to the tumor cells and drug loaded cryogels killed the tumor cells in a time and concentration dependent manner. In vivo studies further confirmed that cryogels could be safely implanted into the brain. Although the implantation of clemastine loaded cryogels did not prevent the growth of the primary tumor, it reduced the amount of invasion tumor cells compared with the mice only resected the tumor. CONCLUSION Cryogels were easily created by the 3D printed templates. The soft material avoided mechanical mismatch with the brain tissue. The cryogel did not show any toxicity in in vitro and in vivo studies, which indicated it would be a promising material to be implanted into the brain.