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具有高度有序结构的骨诱导肽功能化纳米纤维作为骨组织工程的仿生支架

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

作者信息

Gao Xiang, Zhang Xiaohong, Song Jinlin, Xu Xiao, Xu Anxiu, Wang Mengke, Xie Bingwu, Huang Enyi, Deng Feng, Wei Shicheng

机构信息

College of Stomatology, Chongqing Medical University, Chongqing, Beijing, People's Republic of China ; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, Beijing, People's Republic of China.

Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, People's Republic of China.

出版信息

Int J Nanomedicine. 2015 Nov 18;10:7109-28. doi: 10.2147/IJN.S94045. eCollection 2015.

Abstract

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.

摘要

构建能够重现骨组织细胞外基质的拓扑和生化特征的功能性仿生支架,目前是骨组织工程领域的研究热点。在本研究中,通过一步儿茶酚化学法,开发了一种具有高度有序结构的新型表面功能化电纺聚己内酯(PCL)纳米纤维支架,以模拟天然骨组织的关键特征。具体而言,在略碱性水溶液中,静电纺丝后将聚多巴胺(pDA)涂覆在排列好的PCL纳米纤维表面,随后将骨形态发生蛋白-7衍生肽共价固定在pDA涂层的纳米纤维表面。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在细胞粘附、铺展和增殖方面提高纳米纤维的细胞相容性。最重要的是,茜素红S染色、定量实时聚合酶链反应、免疫染色和蛋白质印迹显示,在带有骨诱导肽的排列纳米纤维上培养的人间充质干细胞比在随机取向纳米纤维上培养的细胞表现出更强的成骨分化潜能。此外,带有骨诱导肽的排列纳米纤维即使在没有骨诱导因子的情况下也能引导人间充质干细胞的成骨分化,这表明结合骨诱导肽信号和高度有序纳米纤维优势的仿生设计在细胞命运决定方面具有卓越的成骨功效。所提出的肽修饰骨模拟纳米纤维支架在骨组织工程领域具有广阔的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46df/4655957/f09a56e0131a/ijn-10-7109Fig1.jpg

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