GliaTrap is a biodegradable, non-swelling and non-inflammatory hydrogel with tuned release of CXCL12 to attract migrating glioblastoma cells

A significant factor in relapse and dismal prognosis of glioblastoma is the migrating glioblastoma cells, which diffuse away from the tumor mass into the brain parenchyma. Post-resection application of biomaterials to deliver cytotoxic agents against the invading glioblastoma cells has recently gained attention. The aim of this study was to develop a non-swelling, non-inflammatory biomimetic hydrogel with sustained release of a chemoattractant for glioblastoma cells and perform in vivo proof-of-concept studies to show chemoattraction of invading glioblastoma cells in orthotopic models of human glioblastoma. We used hyaluronic/collagen II-based (HA/Col) hydrogel that incorporates liposomes loaded with CXCL12 to develop GliaTrap. Sustained release of CXCL12 was measured with an ELISA assay. The non-inflammatory properties of GliaTrap were assessed in-vivo after stereotactic implantation in the mouse brain using a cytokine array and immunohistochemistry. The efficacy of GliaTrap on attracting GSCs was determined in-vivo employing 3D light-sheet microscopy on orthotopic human glioblastoma xenografts. We show that GliaTrap is an injectable, non-swelling biomimetic hydrogel that attains sustained release of CXCL12 and does not induce inflammation in the mouse brain. GliaTrap significantly attracts invading glioblastoma cells in orthotopic xenograft models of human glioblastoma as shown with 3D light sheet microscopy. Our findings indicate that GliaTrap can be safely used to attract invading glioblastoma cells by sustained release of a chemoattractant without inducing inflammatory conditions in the brain or local swelling.