Abstract

A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable flexible porous scaffolds were developed via Fused Deposition Modelling (FDM) three-dimensional (3D) printing technology for the local delivery of curcumin. The flexible porous scaffolds were 3D printed with various geometries containing 1, 3, 5, and 7% (w/w) of curcumin, respectively, using curcumin-loaded polycaprolactone (PCL) filaments. The scaffolds were characterised by a series of characterisation studies and in vitro studies were also performed including drug release study, scaffold degradation study, and cytotoxicity study. The curcumin-loaded PCL scaffolds displayed versatile spatiotemporal characteristics. The polymeric scaffolds obtained great mechanical flexibility with a low tensile modulus of less than 2 MPa, and 4 to 7-fold ultimate tensile strain, which can avoid the mechanical mismatch problem of commercially available GLIADEL wafer with a further improvement in surgical margin coverage. In vitro release profiles have demonstrated the sustained release patterns of curcumin with adjustable release amounts and durations up to 77 h. MTT study has demonstrated the great cytotoxic effect of curcumin-loaded scaffolds against the U87 human GBM cell line. Therefore, 3D printed curcumin-loaded scaffold has great promise to provide better GBM treatment options with its mechanical flexibility and customisability to match individual needs, preventing post-surgery GBM recurrence and eventually prolonging the life expectancy of GBM patients.

Highlights

  • Glioblastoma multiforme (GBM) is the most aggressive and lethal form of malignant brain cancer, which, according to the World Health Organisation (WHO), is classified as aGrade IV brain tumour [1,2]

  • Minimum Essential Medium Eagle (MEM), Fetal Bovine Serum (FBS), L-glutamine, Dulbecco’s Phosphate Buffered Saline (PBS), and sodium pyruvate solution were purchased from Sigma-Aldrich (Castle Hill, NSW, Australia)

  • After the solvent casting of curcumin-loaded PCL film and extrusion of curcumin/PCL filament, curcumin-loaded PCL porous scaffolds were Fused Deposition Modelling (FDM) 3D printed curcumin/PCL filament, curcumin-loaded PCL porous scaffolds were FDM 3D printed with different loading doses and geometries, obtaining versatile spatiotemporal characteristics

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Summary

Introduction

Glioblastoma multiforme (GBM) is the most aggressive and lethal form of malignant brain cancer, which, according to the World Health Organisation (WHO), is classified as aGrade IV brain tumour [1,2]. Glioblastoma multiforme (GBM) is the most aggressive and lethal form of malignant brain cancer, which, according to the World Health Organisation (WHO), is classified as a. Despite the optimal treatment of surgical resection followed by radiotherapy and chemotherapy, the five-year survival rate of GBM patients is still less than. The GLIADEL wafer is the most widely used biodegradable polymer-based implant for GBM treatment [7]. GLIADEL wafers are inserted and attached to the resection margin to release Carmustine (BCNU) locally for a week to eliminate residual cancer cells. This kind of local polymeric drug delivery system for implantation

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