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

Abstract

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.

Local delivery to malignant brain tumors: potential biomaterial-based therapeutic/adjuvant strategies

“…Biomaterials Science between the drug device and the soft brain tissue and the associated adverse reactions. 56 Hydrogels also offer an attractive means of delivering biomacromolecules such as proteins and DNA, as such cargoes can be loaded to hydrogels without denaturing hydrophobic interactions. 52 Lastly, hydrogels can be used to deliver chemotherapeutic drugs to GBM by either direct incorporation of the free drug [57][58][59][60][61][62][63] or incorporation of drug-loaded nano/micro carriers 56,[64][65][66] (Fig.…”

Three-Dimensional Printing for Cancer Applications: Research Landscape and Technologies

“…Anticancer drug-loaded hydrogels with a solid disc shape made by extrusion-based printing are able to swell up by two-fold in water within 1 h and provide biphasic drug release for 24 h [ 35 ]. Another implantable hydrogel-based mesh loaded with temozolomide-release microparticles was formulated to prevent the recurrence of glioblastoma after resection surgery [ 36 ].…”

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

“…Three-dimensional (3D) printing is a promising technique for fabricating implantable hydrogels for various biomedical applications [24,[26][27][28][29]. These types of hydrogels have been reported in the literature as a potential scaffold for post-surgery applications in in vivo experiments [30,31].…”