Unal Semra, Arslan Sema, Yilmaz Betul Karademir, Oktar Faik Nuzhet, Ficai Denisa, Ficai Anton, Gunduz Oguzhan
Department of Bioengineering, Faculty of Engineering, Marmara University, 34722 Istanbul, Turkey.
Center for Nanotechnology & Biomaterials Application and Research, Marmara University, 34722 Istanbul, Turkey.
Materials (Basel). 2020 Jun 11;13(11):2661. doi: 10.3390/ma13112661.
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.
胶质母细胞瘤（GBM）是人类脑肿瘤中最恶性的类型之一，对传统治疗具有抗性，且与生存率低相关。由于GBM微环境的三维细胞外基质（ECM）在肿瘤行为中起重要作用，因此对ECM进行工程化将有助于我们获得更多关于肿瘤行为的信息，并确定新的治疗策略。在本研究中，通过静电纺丝成功制备了具有排列和随机取向纳米纤维的聚己内酯（PCL）/明胶（Gel）/透明质酸（HA）复合支架，以模拟GBM肿瘤的细胞外基质。我们研究了纳米形貌和纤维成分对静电纺纳米纤维的机械、形态和亲水性能及其生物相容性的影响。傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）已用于研究各成分之间可能的相互作用。在低收集器转速下，随着HA的存在，纳米纤维基质中的平均纤维直径增加。此外，收集器的旋转速度影响纤维直径及其均匀分布。水接触角测量证实，掺入透明质酸的排列纳米纤维比随机纳米纤维更亲水。此外，与PCL/Gel纳米纤维垫（19.2 MPa）相比，PCL/Gel/HA纳米纤维支架（7.9 MPa）的拉伸强度显著降低。用胶质母细胞瘤细胞（U251）测试了纳米纤维支架的体外生物相容性，具有随机纳米纤维的PCL/Gel/HA支架显示出改善的细胞粘附和增殖。另一方面，发现具有排列纳米纤维的PCL/Gel/HA支架适合增强轴突生长和延伸，支持细胞内通讯。基于这些结果，PCL/Gel/HA复合支架是作为GBM仿生基质和肿瘤研究的优秀候选材料。
