Loading of VEGF to the heparin cross-linked demineralized bone matrix improves vascularization of the scaffold
Loading of VEGF to the heparin cross-linked demineralized bone matrix improves vascularization of the scaffold
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DOI：
10.1007/s10856-009-3827-9
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发表时间：
2010-01-01
影响因子：
3.7
通讯作者：
Dai, Jianwu
中科院分区：
文献类型：
--
作者：
Chen, Lei;He, Zhengquan;Dai, Jianwu
缺乏血管化是多孔组织工程支架的突出缺点之一，导致氧气和营养物质运输不足。在这里，肝素交联脱矿骨基质（HC-DBM）预先加载血管内皮生长因子（VEGF），以促进细胞和新的微血管侵入基质。通过N-羟基琥珀酰亚胺和N-（3-二甲基氨基丙基）-N'-乙基碳二亚胺与肝素化学交联后，支架比未交联的支架能结合更多的VEGF，并实现局部持续递送。VEGF结合肝素化胶原蛋白的生物活性通过促进内皮细胞增殖得到证实。通过皮下植入进一步研究装载VEGF的肝素化DBM的血管生成潜能。血红素-伊红染色及免疫组化观察到载VEGF的肝素化DBM血管生成改善。结果表明，肝素交联DBM结合VEGF可能是刺激细胞和血管侵入支架的有效策略。
Deficient vascularization is one of the prominent shortcomings of porous tissue-engineering scaffolds, which results in insufficient oxygen and nutrients transportation. Here, heparin cross-linked demineralized bone matrices (HC-DBM) pre-loaded with vascular endothelial growth factor (VEGF) were designed to promote cells and new microvessels invasion into the matrices. After being chemical crosslinked with heparin by N-hydroxysuccinimide and N-(3-di-methylaminopropyl)-N'-ethylcarbodiimide, the scaffold could bind more VEGF than the non-crosslinked one and achieve localized and sustained delivery. The biological activity of VEGF binding on heparinized collagen was demonstrated by promoting endothelial cells proliferation. Evaluation of the angiogenic potential of heparinized DBM loaded with VEGF was further investigated by subcutaneous implantation. Improved angiogenesis of heparinized DBM loaded with VEGF was observed from haematoxylin-eosin staining and immunohistochemistry examination. The results demonstrated that heparin cross-linked DBM binding VEGF could be a useful strategy to stimulate cells and blood vessels invasion into the scaffolds.