Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF
Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF
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DOI：
10.1016/j.biomaterials.2016.11.053
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发表时间：
2017-02-01
期刊：
影响因子：
14
通讯作者：
Kim, Hae-Won
中科院分区：
文献类型：
--
作者：
Dashnyam, Khandmaa;Jin, Guang-Zhen;Kim, Hae-Won
生物材料的血管生成能力是在组织修复和再生过程中推动血管向内生长的关键资产。在这里，我们设计了一种独特的基于溶胶-凝胶介孔二氧化硅的血管生成微载体。这种微球在化学结构中“本质上”提供了一种潜在的血管生成刺激剂--硅离子。此外，高度介孔的性质允许血管生成生长因子的‘外部’负载和释放。硅离子在治疗范围内(每天超过几ppm)从微载体中释放，确实上调了HIF1α的表达，并通过阻断HIF-Prolyl羟基酶2(PHD2)来稳定HUVECs。这进而激活了一系列促血管生成分子的表达，包括碱性成纤维细胞生长因子、血管内皮生长因子和eNOS。血管内皮生长因子被有效地结合在微载体的中孔内，然后在几周内持续释放。微载体释放的硅离子和血管内皮生长因子协同刺激内皮细胞的功能，如细胞迁移、趋化归巢和肾小管联网。此外，体内新生血管在鸡绒毛膜尿囊膜模型中的萌发受到Si/VEGF释放微载体的显著促进。本研究通过一个生物相容的介孔微球载体平台展示了硅离子和血管生长因子的协同效应，该概念可能打开一种利用离子和生长因子进行组织修复和再生的新的共载体系统的大门。(C)2016爱思唯尔有限公司。保留所有权利。
Angiogenic capacity of biomaterials is a key asset to drive vascular ingrowth during tissue repair and regeneration. Here we design a unique angiogenic microcarrier based on sol-gel derived mesoporous silica. The microspheres offer a potential angiogenic stimulator, Si ion, 'intrinsically' within the chemical structure. Furthermore, the highly mesoporous nature allows the loading and release of angiogenic growth factor 'extrinsically'. The Si ion is released from the microcarriers at therapeutic ranges (over a few ppm per day), which indeed up-regulates the expression of hypoxia inducing factor 1 alpha(HIF1 alpha) and stabilizes it by blocking HIF-prolyl hydroxylase 2 (PHD2) in HUVECs. This in turn activates the expression of a series of proangiogenic molecules, including bFGF, VEGF, and eNOS. VEGF is incorporated effectively within the mesopores of microcarriers and is then released continuously over a couple of weeks. The Si ion and VEGF released from the microcarriers synergistically stimulate endothelial cell functions, such as cell migration, chemotactic homing, and tubular networking. Furthermore, in vivo neo-blood vessel sprouting in chicken chorioallantoic membrane model is significantly promoted by the Si/VEGF releasing microcarriers. The current study demonstrates the synergized effects of Si ion and angiogenic growth factor through a biocompatible mesoporous microsphere delivery platform, and the concept provided here may open the door to a new co-delivery system of utilizing ions with growth factors for tissue repair and regeneration. (C) 2016 Elsevier Ltd. All rights reserved.