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Hydration of hydrogels regulates vascularization in vivo
Biomaterials Science ( IF 5.8 ) Pub Date : 2017-09-07 00:00:00 , DOI: 10.1039/c7bm00268h Jie Wu 1, 2, 3, 4, 5 , Kunxi Zhang 1, 2, 3, 4 , Xi Yu 1, 2, 3, 4 , Jianxun Ding 4, 5, 6, 7, 8 , Lei Cui 4, 9, 10, 11, 12 , Jingbo Yin 1, 2, 3, 4
Biomaterials Science ( IF 5.8 ) Pub Date : 2017-09-07 00:00:00 , DOI: 10.1039/c7bm00268h Jie Wu 1, 2, 3, 4, 5 , Kunxi Zhang 1, 2, 3, 4 , Xi Yu 1, 2, 3, 4 , Jianxun Ding 4, 5, 6, 7, 8 , Lei Cui 4, 9, 10, 11, 12 , Jingbo Yin 1, 2, 3, 4
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The key barrier to the clinical application of tissue engineering scaffolds is the limitation of rapid and sufficient vascularization. Adipose-derived stem cells (ASCs), especially multicellular aggregates, exhibited a promising angiogenic activity. Herein, we designed a series of poly(L-glutamic acid) (PLGA)-based hydrogels with tunable hydration to control the in situ formation of multicellular spheroids. Oligo(ethylene glycol)s (OEGs) were employed to regulate the hydration of hydrogels. The hydrogel cross-linked with ethylene glycol (OEG1) supported the most excellent adhesion and proliferation of human ASCs in vitro. However, as the hydration of hydrogels strengthened, the adherent ASCs were gradually replaced with multicellular spheroids. Moreover, the in situ formation of spheroids was more effective in upregulating hypoxia-adaptive signals (e.g., hypoxia-inducible factor-1α, HIF-1α) and enhancing the secretion of angiogenic factors (e.g., vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2)) compared to adherent cells in OEG1 hydrogels. The hydrogel cross-linked with oligo(ethylene glycol)400 (OEG9) carrying spheroids induced a high angiogenic response of host tissue in vivo, resulting in an improved system vascularization, compared to adherent cells in the OEG1 hydrogel. These features indicated that the PLGA-based hydrogels were expected to be applied toward bone and fat tissue regeneration.
中文翻译：
水凝胶的水化调节体内血管生成
组织工程支架临床应用的主要障碍是快速和充分血管化的局限性。脂肪干细胞（ASC），特别是多细胞聚集体，显示出有希望的血管生成活性。本文中，我们设计了一系列具有可调水合作用的聚L-谷氨酸（PLGA）基水凝胶，以控制多细胞球体的原位形成。寡聚乙二醇（OEG）用于调节水凝胶的水合作用。与乙二醇（OEG 1）交联的水凝胶支持体外人类ASC的最优异粘附和增殖。但是，随着水凝胶水合作用的增强，粘附的ASC逐渐被多细胞球体所取代。此外，球状体的原位形成在上调缺氧适应性信号（如缺氧诱导因子-1α，HIF-1α）和增强血管生成因子（如血管内皮生长因子（VEGF）和成纤维细胞）的分泌方面更有效。与OEG 1水凝胶中的贴壁细胞相比，其生长因子2（FGF-2）的含量更高。与OEG中的贴壁细胞相比，与带有球体的低聚（乙二醇）400（OEG 9）交联的水凝胶在体内诱导了宿主组织的高血管生成反应，从而改善了系统血管形成1个水凝胶。这些特征表明，预期将基于PLGA的水凝胶应用于骨骼和脂肪组织的再生。
更新日期：2017-10-24
中文翻译：
水凝胶的水化调节体内血管生成
组织工程支架临床应用的主要障碍是快速和充分血管化的局限性。脂肪干细胞（ASC），特别是多细胞聚集体，显示出有希望的血管生成活性。本文中，我们设计了一系列具有可调水合作用的聚L-谷氨酸（PLGA）基水凝胶，以控制多细胞球体的原位形成。寡聚乙二醇（OEG）用于调节水凝胶的水合作用。与乙二醇（OEG 1）交联的水凝胶支持体外人类ASC的最优异粘附和增殖。但是，随着水凝胶水合作用的增强，粘附的ASC逐渐被多细胞球体所取代。此外，球状体的原位形成在上调缺氧适应性信号（如缺氧诱导因子-1α，HIF-1α）和增强血管生成因子（如血管内皮生长因子（VEGF）和成纤维细胞）的分泌方面更有效。与OEG 1水凝胶中的贴壁细胞相比，其生长因子2（FGF-2）的含量更高。与OEG中的贴壁细胞相比，与带有球体的低聚（乙二醇）400（OEG 9）交联的水凝胶在体内诱导了宿主组织的高血管生成反应，从而改善了系统血管形成1个水凝胶。这些特征表明，预期将基于PLGA的水凝胶应用于骨骼和脂肪组织的再生。
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