Enhanced angiogenesis of porous collagen scaffolds by incorporation of TMC/DNA complexes encoding vascular endothelial growth factor
Enhanced angiogenesis of porous collagen scaffolds by incorporation of TMC/DNA complexes encoding vascular endothelial growth factor
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DOI：
10.1016/j.actbio.2009.04.004
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发表时间：
2009-10-01
影响因子：
9.7
通讯作者：
Shen, Jiacong
中科院分区：
文献类型：
--
作者：
Mao, Zhengwei;Shi, Haifei;Shen, Jiacong
植入结构的血管生成是组织工程和再生医学中最重要的问题之一，通常可能需要长达数周的时间。血管内皮生长因子（VEGF）对增强体内血管生成具有积极作用。但生长因子的掺入有许多局限性，因为它们的半衰期通常只有几分钟。因此，在这项工作中，编码 VEGF 的 DNA 被应用于增强胶原支架的血管生成。使用阳离子基因递送载体 N,N,N-三甲基氯化壳聚糖 (TMC) 与编码 VEGF 的质粒 DNA 形成复合物。然后将复合物掺入胶原蛋白支架中，负载由补料浓度介导并以持续的方式释放。体外细胞培养表明，含有支架的 TMC/DNA 复合物，特别是含有大量 DNA 的 VEGF 表达水平显着提高。将含有TMC/DNA复合物的支架皮下植入Sprague-Dawley小鼠体内，通过肉眼观察、苏木精-伊红染色和免疫组织化学染色研究其血管生成。结果表明，TMC/DNA复合物的掺入可以有效增强体内VEGF表达，从而增强植入支架的血管生成。 (C) 2009 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
Angiogenesis of an implanted construct is one of the most important issues in tissue engineering and regenerative medicine, and can often take as long as several weeks. The vascular endothelial growth factor (VEGF) shows a positive effect on enhancing angiogenesis in vivo. But the incorporation of growth factors has many limitations, since they typically have half-lives only on the order of minutes. Therefore, in this work the DNA encoding VEGF was applied to enhance the angiogenesis of a collagen scaffold. A cationic gene delivery vector, N,N,N-trimethyl chitosan chloride (TMC), was used to form complexes with the plasmid DNA encoding VEGF. The complexes were then incorporated into the collagen scaffold, the loading being mediated by the feeding concentration and release in a sustained manner. In vitro cell culture demonstrated a significant improvement in the VEGF expression level from the TMC/DNA complexes containing scaffolds, in particular with a large amount of DNA. The scaffolds containing the TMC/DNA complexes were subcutaneously implanted into Sprague-Dawley mice to study their angiogenesis via macroscopic observation, hematoxylin-eosin staining and immunohistochemical staining. The results demonstrated that the incorporation of TMC/DNA complexes could effectively enhance the in vivo VEGF expression and thereby the angiogenesis of implanted scaffolds. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.