Dual release of growth factor from nanocomposite fibrous scaffold promotes vascularisation and bone regeneration in rat critical sized calvarial defect
Dual release of growth factor from nanocomposite fibrous scaffold promotes vascularisation and bone regeneration in rat critical sized calvarial defect
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DOI：
10.1016/j.actbio.2018.07.050
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发表时间：
2018-09-15
影响因子：
9.7
通讯作者：
Tabata, Yasuhiko
中科院分区：
文献类型：
--
作者：
Kuttappan, Shruthy;Mathew, Dennis;Tabata, Yasuhiko
一个有前途的策略，增加骨形成涉及多种骨诱导和血管生成生长因子的局部交付。然而，成功取决于持续的生长因子释放及其适当的组合，以诱导骨部位的干细胞和成骨细胞。在此，我们开发了一种纳米复合纤维支架，其装载有成纤维细胞生长因子2（FGF 2）、血管内皮生长因子（VEGF）和骨形态发生蛋白2（BMP 2），并将其在临界尺寸的颅骨缺损中促进血管形成和骨再生的能力与具有VEGF + BMP 2和FGF 2 + BMP 2的支架进行了比较。生长因子在支架上的简单负载可以提供体外和体内的差异释放模式（VEGF释放1周，而BMP 2和FGF 2释放3周）。在所有组中，双生长因子负载的支架（VEGF + BMP 2和FGF 2 + BMP 2）促进血管化和新骨形成，但在FGF 2和VEGF负载的支架之间没有差异，尽管其释放模式不同。FGF 2主要促进干细胞迁移，而VEGF增强缺损部位的新血管形成。这项研究表明，仿生纳米复合支架是一个有前途的生长因子载体，以促进骨再生在critical sized bone deficiency.Statement的显著性许多研究表明，生长因子，如VEGF-BMP 2或FGF 2-BMP 2在促进骨形成在critical sized bone deficiency. Statement的影响，但有没有报告表明，直接比较VEGF-BMP 2和FGF 2-BMP 2。在这项研究中，我们开发了一种纳米复合纤维支架，可以差异释放生长因子，如VEGF，BMP 2和FGF 2（VEGF释放1周，而BMP 2和FGF 2释放3周），这反过来又促进了关键尺寸缺损中的新血管形成和新骨形成。VEGF + BMP 2或FGF 2 + BMP 2诱导的血管形成和骨形成没有差异。生长因子以简单的方式加载，这将确保最终用户的易用性，特别是对于在手术室中治疗患者的外科医生。(C)2018 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
A promising strategy for augmenting bone formation involves the local delivery of multiple osteoinductive and vasculogenic growth factors. However, success depends on sustained growth factor release and its appropriate combination to induce stem cells and osteogenic cells at the bony site. Herein, we have developed a nanocomposite fibrous scaffold loaded with fibroblast growth factor 2 (FGF2), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) and its ability to promote vascularisation and bone regeneration in critical sized calvarial defect was compared to the scaffold with VEGF + BMP2 and FGF2 + BMP2. Simple loading of growth factors on the scaffold could provide a differential release pattern, both in vitro and in vivo (VEGF release for 1 week where as BMP2 and FGF2 release for 3 weeks). Among all the groups, dual growth factor loaded scaffold (VEGF + BMP2 & FGF2 + BMP2) enhanced vascularisation and new bone formation, but there was no difference between FGF2 and VEGF loaded scaffolds although its release pattern was different. FGF2 mainly promoted stem cell migration, whereas VEGF augmented new blood vessel formation at the defect site. This study suggests that biomimetic nanocomposite scaffold is a promising growth factor delivery vehicle to improve bone regeneration in critical sized bone defects.Statement of SignificanceMany studies have shown the effect of growth factors like VEGF-BMP2 or FGF2-BMP2 in enhancing bone formation in critical sized defects, but there are no reports that demonstrate the direct comparison of VEGF-BMP2 and FGF2-BMP2. In this study, we have developed a nanocomposite fibrous scaffold that could differentially release growth factors like VEGF, BMP2 and FGF2 (VEGF release for 1 week where as BMP2 and FGF2 release for 3 weeks), which in turn promoted neovascularisation and new bone formation in critical sized defects. There was no difference in vascularisation and bone formation induced by VEGF + BMP2 or FGF2 + BMP2. The growth factor was loaded in a simple manner, which would ensure ease of use for the end-user, especially for the surgeons treating a patient in an operating room. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.