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A 3D bioprinted hydrogel mesh loaded with all-trans retinoic acid for treatment of glioblastoma

Bahram Mirani^1,2,3, Erik Pagana¹, Shahla Shojaei^1,2,3, Jade Duchscherera¹, Brian D. Toyota⁴, Saeid Ghavamie^5,6,7, Mohsen Akbari^1,2,3*

1 Laboratory for Innovations in Microengineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada

2 Centre for Advanced Materials and Related Technologies (CAMTEC), University of Victoria, Victoria, BC, V8P 5C2, Canada

3 Centre for Biomedical Research (CBR), University of Victoria, Victoria, BC, V8P 5C2, Canada

4 Division of Neurosurgery, Faculty of Medicine, Queen’s University, Kingston, ON, K7K 1G8, Canada

5 Department of Human Anatomy and Cell Sciences, Faculty of Health Science, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada

6 Autophagy Research Center, Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran

7 Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB, Canada

PUBLISHED IN: European Journal of Pharmacology, 854, 2019

ABSTRACT

Treatment of glioblastoma (GBM), as the most lethal type of brain tumor, still remains a major challenge despite the various therapeutic approaches developed over the recent decades. GBM is considered as one of the most therapy-resistant human tumors. Treatment with temozolomide (TMZ) chemotherapy and radiotherapy in GBM patients has led to 30% of two-year survival rate (American Brain Tumor Association), representing a demanding field to develop more effective therapeutic strategies. This study presents a novel method for local delivery of all-trans retinoic acid (ATRA) for targeting GBM cells as a possible adjuvant therapeutic strategy for this disease. We have used 3D bioprinting to fabricate hydrogel meshes laden with ATRA-loaded polymeric particles. The ATRA-loaded meshes have been shown to facilitate a sustained release of ATRA with tunable release rate. Cell viability assay was used to demonstrate the ability of fabricated meshes in reducing cell growth in U-87 MG cell line. We later showed that the developed meshes induced apoptotic cell death in U-87 MG. Furthermore, the use of hydrogel for embedding the ATRA-loaded particles can facilitate the immobilization of the drug next to the tumor site. Our current innovative approach has shown the potential to open up new avenues for treatment of GBM, benefiting patients who suffer from this debilitating disease.

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