Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
Yuzuncuyil Hospital, Ankara 06530, Turkey.
Biomater Sci. 2016 Aug 16;4(9):1328-39. doi: 10.1039/c6bm00179c.
Biomineralization of the extracellular matrix (ECM) plays a crucial role in bone formation. Functional and structural biomimetic native bone ECM components can therefore be used to change the fate of stem cells and induce bone regeneration and mineralization. Glycosaminoglycan (GAG) mimetic peptide nanofibers can interact with several growth factors. These nanostructures are capable of enhancing the osteogenic activity and mineral deposition of osteoblastic cells, which is indicative of their potential application in bone tissue regeneration. In this study, we investigated the potential of GAG-mimetic peptide nanofibers to promote the osteogenic differentiation of rat mesenchymal stem cells (rMSCs) in vitro and enhance the bone regeneration and biomineralization process in vivo in a rabbit tibial bone defect model. Alkaline phosphatase (ALP) activity and Alizarin red staining results suggested that osteogenic differentiation is enhanced when rMSCs are cultured on GAG-mimetic peptide nanofibers. Moreover, osteogenic marker genes were shown to be upregulated in the presence of the peptide nanofiber system. Histological and micro-computed tomography (Micro-CT) observations of regenerated bone defects in rabbit tibia bone also suggested that the injection of a GAG-mimetic nanofiber gel supports cortical bone deposition by enhancing the secretion of an inorganic mineral matrix. The volume of the repaired cortical bone was higher in GAG-PA gel injected animals. The overall results indicate that GAG-mimetic peptide nanofibers can be utilized effectively as a new bioactive platform for bone regeneration.
细胞外基质（ECM）的生物矿化在骨形成中起着至关重要的作用。因此，功能性和结构性仿生天然骨 ECM 成分可用于改变干细胞的命运，诱导骨再生和矿化。糖胺聚糖（GAG）模拟肽纳米纤维可以与多种生长因子相互作用。这些纳米结构能够增强成骨细胞的成骨活性和矿化沉积，表明它们在骨组织再生中有潜在的应用。在这项研究中，我们研究了 GAG 模拟肽纳米纤维在体外促进大鼠间充质干细胞（rMSCs）成骨分化的潜力，并在兔胫骨骨缺损模型中增强体内骨再生和生物矿化过程。碱性磷酸酶（ALP）活性和茜素红染色结果表明，当 rMSCs 在 GAG 模拟肽纳米纤维上培养时，成骨分化得到增强。此外，在肽纳米纤维系统存在的情况下，成骨标记基因的表达上调。对兔胫骨骨再生骨缺损的组织学和微计算机断层扫描（Micro-CT）观察也表明，GAG 模拟纳米纤维凝胶的注射通过增强无机矿物基质的分泌，支持皮质骨沉积。注射 GAG-PA 凝胶的动物修复皮质骨的体积更高。总体结果表明，GAG 模拟肽纳米纤维可用作骨再生的新型生物活性平台。
