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Loading of VEGF to the heparin cross-linked demineralized bone matrix improves vascularization of the scaffold

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Abstract

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.

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Acknowledgments

The authors thank Dr. Hang Lin, Ms. Xia Wang and Ms. Jin Han from Dai Lab for invaluable comments, and Ms Juan Fan and Mr Xianglin Hou from Dai Lab for their technical assistance. This work was supported by grants from National Natural Science Foundation of China (30688002; 30600304), the Ministry of Science and Technology of China (2006CB943601), Chinese Academy of Sciences (KSCX2-YW-R-133) and K. C. Wang Education Foundation.

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Authors and Affiliations

  1. Biotechnology Research Center, Hubei Province Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, 443002, People’s Republic of China

    Lei Chen & Zhengquan He

  2. Department of Oral and Maxillofacial Surgery, Daping Hospital, Research Institute of Sugery, Third Military Medical University, Chongqing, 400042, People’s Republic of China

    Maojin Yang

  3. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China

    Bing Chen, Yannan Zhao, Wenjie Sun, Zhifeng Xiao, Jing Zhang & Jianwu Dai

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  1. Lei Chen
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Correspondence to Jianwu Dai.

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These authors contributed equally to this work.

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Chen, L., He, Z., Chen, B. et al. Loading of VEGF to the heparin cross-linked demineralized bone matrix improves vascularization of the scaffold. J Mater Sci: Mater Med 21, 309–317 (2010). https://doi.org/10.1007/s10856-009-3827-9

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  • DOI: https://doi.org/10.1007/s10856-009-3827-9

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