Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF
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- 作者：Khandmaa Dashnyama ; b ; Guang-Zhen Jina ; b ; Joong-Hyun Kima ; b ; Roman Pereza ; b ; c ; Jun-Hyeog Jangd ; Hae-Won Kima ; b ; e ; f ; kimhw@dku.edu
- 关键词：Angiogenesis ; Co-delivery ; Silicon ion ; VEGF ; Mesoporous ; Microsphere
- 刊名：Biomaterials
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：116
- 期：Complete
- 页码：145-157
- 全文大小：3696 K
- 卷排序：116
文摘
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 1α (HIF1α) 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.