Polycaprolactone/Gelatin/Hyaluronic Acid Electrospun Scaffolds to Mimic Glioblastoma Extracellular Matrix

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.

Development of Inula graveolens (L.) Plant Extract Electrospun/Polycaprolactone Nanofibers: A Novel Material for Biomedical Application

“…Natural polymers from green plants are renewable [11,12]. Electrospinning of a polycaprolactone (PCL)/gelatin(Gel)/hyaluronic acid(HA) blended solution composite scaffold has been shown in recent studies to be an efficient technique for modifying PCL nanofibrous scaffolds for 3D glioblastoma cell culture [13]. Polycaprolactone (PCL), silver nitrate (AgNO3) and zinc oxide (ZnO) were used for the fabrication of a multilayered antibacterial nanocomposite material using coaxial electrospinning (CAE) as described by Guner CETIN et al [14].…”

Altering the characterization of nanofibers by changing the electrospinning parameters and their application in tissue engineering, drug delivery, and gene delivery systems

“…Hence, many researchers focus on designing scaffolds with similar properties to human tissue on a nanoscale. Several studies have reported that large‐scale electrospinning can be produced using three‐dimensional connected porous nanofiber structures to resemble a native ECM network 136,137 . Gholipour Malekabadi et al designed new electrospun nanofiber scaffolds using electrospinning of different concentrations of silk fibroin solutions and evaluated their application for tissue engineering both in vitro and in vivo.…”

Glycomaterials to Investigate the Functional Role of Aberrant Glycosylation in Glioblastoma

“…[225][226][227][228] Synthetic materials such as PEG, alginate, PCL, polystyrene, polyacrylonitrile, and PDMS have been used as scaffolds and platforms to assess GBM migration and invasion, for their reproducibility and tunable mechanical properties. [229][230][231] However, because these materials lack biological recognition sites, they need to be functionalized with adhesive peptides or proteins to facilitate cell adhesion and growth. Alternatively, hybrid approaches that combine the biomimetic attributes of natural polymers with the tunable properties of synthetic poly-mers overcome these limitations in evaluating GBM invasion and therapeutic resistance.…”