Journal
BIOMATERIALS
Volume 33, Issue 7, Pages 2076-2085Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.11.042
Keywords
Hypoxia; Mesoporous bioactive glass; Bone tissue engineering; VEGF secretion; HIF-1 alpha expression
Funding
- Natural Science Foundation of China [30730034]
- One Hundred Talent Project
- SIC-CAS
- QUT
- ARC [DP120103697]
- Prince Charles Hospital Foundation [MS2011-05]
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Low oxygen pressure (hypoxia) plays an important role in stimulating angiogenesis; there are, however, few studies to prepare hypoxia-mimicking tissue engineering scaffolds. Mesoporous bioactive glass (MBG) has been developed as scaffolds with excellent osteogenic properties for bone regeneration. Ionic cobalt (Co) is established as a chemical inducer of hypoxia-inducible factor (HIF)-1 alpha, which induces hypoxia-like response. The aim of this study was to develop hypoxia-mimicking MBG scaffolds by incorporating ionic Co2+ into MBG scaffolds and investigate if the addition of Co2+ ions would induce a cellular hypoxic response in such a tissue engineering scaffold system. The composition, microstructure and mesopore properties (specific surface area, nano-pore volume and nano-pore distribution) of Co-containing MBG (Co-MBG) scaffolds were characterized and the cellular effects of Co on the proliferation, differentiation, vascular endothelial growth factor (VEGF) secretion, HIF-1 alpha expression and bone-related gene expression of human bone marrow stromal cells (BMSCs) in MBG scaffolds were systematically investigated. The results showed that low amounts of Co (<5%) incorporated into MBG scaffolds had no significant cytotoxicity and that their incorporation significantly enhanced VEGF protein secretion, HIF-1 alpha expression, and bone-related gene expression in BMSCs, and also that the Co-MBG scaffolds support BMSC attachment and proliferation. The scaffolds maintain a well-ordered mesopore channel structure and high specific surface area and have the capacity to efficiently deliver antibiotics drugs: in fact, the sustained released of ampicillin by Co-MBG scaffolds gives them excellent anti-bacterial properties. Our results indicate that incorporating cobalt ions into MEG scaffolds is a viable option for preparing hypoxia-mimicking tissue engineering scaffolds and significantly enhanced hypoxia function. The hypoxia-mimicking MBG scaffolds have great potential for bone tissue engineering applications by combining enhanced angiogenesis with already existing osteogenic properties. (C) 2011 Elsevier Ltd. All rights reserved.
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