Dual-peptide-modified alginate hydrogels for the promotion of angiogenesis
Dual-peptide-modified alginate hydrogels for the promotion of angiogenesis
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DOI：
10.1007/s11426-015-5451-5
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发表时间：
2015-07
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影响因子：
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通讯作者：
Yanyan Yu;Lei Guo;Wei Wang;Jina Wu;Zhi Yuan
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文献类型：
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作者：
Yanyan Yu;Lei Guo;Wei Wang;Jina Wu;Zhi Yuan
提供合适血管系统的能力是人工厚组织工程的主要挑战。血管生成是微血管形成过程中的关键环节。许多生物活性分子如细胞外基质（ECM）蛋白和来源于ECM的粘附肽被用于促进血管生成。本研究选用两种粘附肽YIGSR和REDV对海藻酸钠（ALG）进行修饰，得到YIGSR-海藻酸钠偶联物（ALG-YIGSR）和REDV-海藻酸钠偶联物（ALG-REDV）。我们将两种肽偶联物按一定浓度比例混合制备了用于体外研究的生物活性表面和用于体内研究的水凝胶支架，体外研究表明，1.09 pmol/mm ~ 2肽修饰的表面与人脐静脉内皮细胞（HUVECs）的亲和性最好，而高浓度或低浓度的肽修饰的表面与HUVECs的亲和性最差。此外，双肽修饰的表面能显著促进HUVECs的增殖，其中ALG-YIGSR：ALG-REDV摩尔比为5：1时的促进作用最强。此外，体内血管生成结果表明，由ALG-YIGSR和ALG-REDV以5：1的比例混合组成的水凝胶支架具有通过刺激新血管形成的血管生成诱导潜力，并且显示出比由单一肽组成的支架更高的血管密度。这些结果表明，肽藻酸盐缀合物的混合组合可以是在组织工程应用中刺激和诱导血管生成的潜在支架。
The ability to supply suitable blood vessel system is a major challenge for artificial thick tissue engineering. Angiogenesis is a key point during the process of microvascular formation. Many bioactive molecules such as extra cellular matrix (ECM) proteins and adhesion peptides derived from the ECM are applied to promote angiogenesis. In this work, two adhesion peptides, YIGSR and REDV, were selected to modify sodium alginate (ALG) to obtain YIGSR- and REDV-alginate conjugates (ALG-YIGSR, and ALG-REDV, respectively). We mixed the two peptide-conjugates together in a series of concentration ratios to prepare bioactive surfaces forin vitrostudies and hydrogel scaffolds forin vivostudies.In vitrostudies showed that surfaces modified with 1.09 pmol/mm2peptide had the best affinity to human umbilical vein endothelial cells (HUVECs) than that with high or low concentrations of peptides. In addition, surfaces modified with dual peptides could significantly promote HUVECs proliferation, where ALG-YIGSR:ALG-REDV at a mole ratio of 5:1 exhibited the best enhancement ability. Furthermore, thein vivoangiogenesis results demonstrated that hydrogel scaffolds composed of mixed ALG-YIGSR and ALG-REDV at the 5:1 ratio had angiogenic induction potential by stimulating new blood vessel formation, and showed higher blood vessel density than scaffolds composed of a single peptide. These results demonstrated that a mixed combination of peptide alginate conjugates could be a potential scaffold to stimulate and induce angiogenesis in tissue engineering applications.