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Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

机译:具有高度有序结构的骨诱导肽功能化纳米纤维作为用于骨组织工程的仿生支架

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摘要

The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering.
机译:概述骨组织细胞外基质的拓扑和生化特征的功能仿生支架的构建现在在骨组织工程中受到关注。在这项研究中,开发了一种新型的具有高度有序结构的表面功能化电纺聚己内酯(PCL)纳米纤维支架,以通过邻苯二酚化学的一个步骤模拟天然骨组织的关键特征。特别是,在弱碱性水溶液下,电纺丝后将聚多巴胺(pDA)涂覆在对齐的PCL纳米纤维的表面上,然后将骨形态发生蛋白7衍生的肽共价固定在pDA涂覆的纳米纤维表面上。接触角测量,拉曼光谱和X射线光电子能谱证实了PCL纳米纤维表面上存在pDA和肽。我们的结果表明,用骨诱导肽进行表面修饰可以提高纳米纤维在细胞粘附,扩散和增殖方面的细胞相容性。最重要的是,茜素红S染色,实时荧光定量定量聚合酶链反应,免疫染色和Western印迹显示,在具有骨诱导肽的对齐纳米纤维上培养的人间充质干细胞比随机取向的纳米纤维上的细胞具有更高的成骨分化潜能。此外,即使在没有骨诱导因子的情况下,与骨诱导肽对齐的纳米纤维也可以指导人间充质干细胞的成骨分化,这表明仿生设计具有优异的成骨功效,结合了骨诱导肽信号和高度有序的纳米纤维对细胞命运决定的优势。提出的肽修饰的骨模拟纳米纤维支架在骨组织工程的背景下具有前途的潜力。

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