A Drug-Eluting 3D-Printed Mesh (GlioMesh) for Management of Glioblastoma

Current treatment strategies for Glioblastoma (GBM)-including surgery, radiotherapy, and chemotherapy with oral administration of temozolomide (TMZ)-still lead to poor survival rates, making the development of more effective therapeutic methods an urgent need. This study presents a new approach for the treatment of GBM patients using a 3D-printed hydrogel-based mesh (GlioMesh), loaded with TMZ-releasing microparticles, that is capable of delivering TMZ over several weeks at the tumor site. Given the challenges associated with loading the amphiphilic TMZ in polymeric substrates, a novel encapsulation strategy is developed using an oil-in-oil emulsion method that improves the encapsulation efficiencies of TMZ in poly(lactic-co-glycolic acid) (PLGA) from <7% to about 61%. The cytotoxic effects of GlioMesh on GBM cells are evaluated in vitro by investigating the resultant levels of DNA break, autophagic activity, and mitochondrial damage. It is shown that GlioMesh produces significantly higher susceptibility to the drug in comparison with free TMZ by maintaining the level of autophagic activity and inducing larger degrees of mitochondrial damage. Sustained delivery of TMZ holds promise for suppressing chemoresistance to TMZ that is normally developed in GBM cells in systemic administration of the drug due to the induction of autophagy.