Abstract
Glioblastoma (GBM), one of the most malignant types of human brain tumor, is resistant to conventional treatments and is associated with poor survival. Since the 3D extracellular matrix (ECM) of GBM microenvironment plays a significant role on the tumor behavior, the engineering of the ECM will help us to get more information on the tumor behavior and to define novel therapeutic strategies. In this study, polycaprolactone (PCL)/gelatin(Gel)/hyaluronic acid(HA) composite scaffolds with aligned and randomly oriented nanofibers were successfully fabricated by electrospinning for mimicking the extracellular matrix of GBM tumor. We investigated the effect of nanotopography and components of fibers on the mechanical, morphological, and hydrophilic properties of electrospun nanofiber as well as their biocompatibility properties. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) have been used to investigate possible interactions between components. The mean fiber diameter in the nanofiber matrix was increased with the presence of HA at low collector rotation speed. Moreover, the rotational velocity of the collector affected the fiber diameters as well as their homogenous distribution. Water contact angle measurements confirmed that hyaluronic acid-incorporated aligned nanofibers were more hydrophilic than that of random nanofibers. In addition, PCL/Gel/HA nanofibrous scaffold (7.9 MPa) exhibited a significant decrease in tensile strength compared to PCL/Gel nanofibrous mat (19.2 MPa). In-vitro biocompatibilities of nanofiber scaffolds were tested with glioblastoma cells (U251), and the PCL/Gel/HA scaffolds with random nanofiber showed improved cell adhesion and proliferation. On the other hand, PCL/Gel/HA scaffolds with aligned nanofiber were found suitable for enhancing axon growth and elongation supporting intracellular communication. Based on these results, PCL/Gel/HA composite scaffolds are excellent candidates as a biomimetic matrix for GBM and the study of the tumor.
Highlights
Glioblastoma (GBM) is a highly malignant human primary brain tumor
Electrospinning is a simple and commonly used technique for constructing 3D scaffolds consisting of nanofibers or mostly sub-microfibers-structured scaffolds [5,6,7] that closely mimic the dimensions of collagen fibril of GBM extracellular matrix (ECM) [8,9]
The PCL/Gel nanofiber diameter obtained from the electrospinning of the mixture solution of formic/acetic acid was found lower to that fabricated by other studies that used conventional halogenated solvents [14]
Summary
Glioblastoma (GBM) is a highly malignant human primary brain tumor. Even with maximal surgical resection followed by adjuvant chemo-radiotherapy, median survival is still less than two years [1]. Instead of the cell monolayer culture in the petri dish, the use of 3D scaffolds that mimic the ECM of the tumor can provide several advantages, such as mirroring the environment in which tumor cells live in the body, better replicating complex tissue structures. It reflects normal differentiation, cell behavior, and intercellular interactions; shows more realistic cell biology and function; and provides more accurate predictions of the disease states and drug response. By combining gelatin with PCL, a composite scaffold having good mechanical strength, enhanced cell adhesion, and cell growth properties can be fabricated [15,16,17]
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