Zhang Kuihua, Zheng Honghao, Liang Su, Gao Changyou
College of Materials and Textile Engineering, Jiaxing University, Jiaxing 314001, China; MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310007, China.
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310007, China.
Acta Biomater. 2016 Jun;37:131-42. doi: 10.1016/j.actbio.2016.04.008. Epub 2016 Apr 7.
The graphene oxide (GO) has attracted tremendous attention in biomedical fields. In order to combine the unique physicochemical properties of GO nanosheets with topological structure of aligned nanofibrous scaffolds for nerve regeneration, the GO nanosheets were coated onto aligned and aminolyzed poly-l-lactide (PLLA) nanofibrous scaffolds. Scanning electronic microscopy (SEM) and atomic force microscopy (AFM) revealed that the surface of aligned PLLA nanofibers after being coated with GO became rougher than those of the aligned PLLA and aminolyzed PLLA nanofibrous scaffolds. The GO nanosheets did not destroy the alignment of nanofibers. The characterizations of X-ray photoelectron spectroscopy (XPS) and water contact angle displayed that the aligned PLLA nanofibrous scaffolds were introduced with hydrophilic groups such as NH2, COOH, and OH after aminolysis and GO nanosheets coating, showing better hydrophilicity. The GO-coated and aligned PLLA nanofibrous scaffolds significantly promoted Schwann cells (SCs) proliferation with directed cytoskeleton along the nanofibers compared with the aligned PLLA and aminolyzed PLLA nanofibrous scaffolds. These scaffolds also greatly improved the proliferation of rat pheochromocytoma 12 (PC12) cells, and significantly promoted their differentiation and neurite growth along the nanofibrous alignment in the presence of nerve growth factor (NGF). This type of scaffolds with nanofibrous surface topography and GO nanosheets is expected to show better performance in nerve regeneration.
Recovery of damaged nerve functions remains a principal clinical challenge in spite of surgical intervention and entubulation. The use of aligned fibrous scaffolds provides suitable microenvironment for nerve cell attachment, proliferation and migration, enhancing the regeneration outcome of nerve tissue. Surface modification is generally required for the synthetic polymeric fibers by laminin, fibronectin and YIGSR peptides to stimulate specific cell functions and neurite outgrowth. Yet these proteins or peptides present the poor processibility, limited availability, and high cost, influencing their application in clinic. In this work, we combined GO nanosheets and topological structure of aligned nanofibrous scaffolds to direct cell migration, proliferation, and differentiation, and to induce neurite outgrowth for nerve regeneration. The GO coating improved several biomedical properties of the aligned PLLA nanofibrous scaffolds including surface roughness, hydrophilicity and promotion of cells/material interactions, which significantly promoted SCs growth and regulated cell orientation, and induced PC12 cells differentiation and neurite growth. The design of this type of structure is of both scientific and technical importance, and possesses broad interest in the fields of biomaterials, tissue engineering and regenerative medicine.
氧化石墨烯(GO)在生物医学领域引起了极大关注。为了将GO纳米片独特的物理化学性质与用于神经再生的排列纳米纤维支架的拓扑结构相结合,将GO纳米片涂覆在排列并经氨基解聚的聚左旋乳酸(PLLA)纳米纤维支架上。扫描电子显微镜(SEM)和原子力显微镜(AFM)显示,涂覆GO后排列的PLLA纳米纤维表面比排列的PLLA和经氨基解聚的PLLA纳米纤维支架表面更粗糙。GO纳米片没有破坏纳米纤维的排列。X射线光电子能谱(XPS)和水接触角表征表明,经氨基解聚和GO纳米片涂覆后,排列的PLLA纳米纤维支架引入了诸如NH2、COOH和OH等亲水性基团,显示出更好的亲水性。与排列的PLLA和经氨基解聚的PLLA纳米纤维支架相比,涂覆GO且排列的PLLA纳米纤维支架显著促进了雪旺细胞(SCs)的增殖,其细胞骨架沿纳米纤维定向排列。这些支架还极大地促进了大鼠嗜铬细胞瘤12(PC12)细胞的增殖,并在神经生长因子(NGF)存在的情况下显著促进其分化和沿纳米纤维排列方向的神经突生长。这种具有纳米纤维表面形貌和GO纳米片的支架有望在神经再生中表现出更好的性能。
尽管有手术干预和插管,但受损神经功能的恢复仍然是主要的临床挑战。使用排列的纤维支架为神经细胞附着、增殖和迁移提供了合适的微环境,提高了神经组织的再生效果。合成聚合物纤维通常需要通过层粘连蛋白、纤连蛋白和YIGSR肽进行表面修饰,以刺激特定的细胞功能和神经突生长。然而,这些蛋白质或肽的加工性能差、可用性有限且成本高,影响了它们在临床上的应用。在这项工作中,我们将GO纳米片与排列的纳米纤维支架的拓扑结构相结合,以引导细胞迁移、增殖和分化,并诱导神经突生长用于神经再生。GO涂层改善了排列的PLLA纳米纤维支架的几种生物医学特性,包括表面粗糙度、亲水性以及促进细胞/材料相互作用,这显著促进了SCs的生长并调节了细胞取向,并诱导了PC12细胞的分化和神经突生长。这种结构的设计具有科学和技术重要性,并且在生物材料、组织工程和再生医学领域具有广泛的兴趣。