The key barrier to clinical applications 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 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, the adherent ASCs were gradually replaced with multicellular spheroids in higher hydration of hydrogels. Moreover, the in situ formation of spheroids was more effective to upregulate hypoxia-adaptive signals (e.g., hypoxia-inducible factor-1α, HIF-1α) and enhance secretion of angiogenic factors (e.g., vascular endothelial growth and 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 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。在这里，我们设计了一系列基于聚（L-谷氨酸）（PLGA）的水凝胶，这些水凝胶具有可调节的水合作用，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（OEG1）交联的水凝胶在体外支持人类ASC的最优异粘附和增殖。然而，在水凝胶更高的水合作用中，粘附的ASCs逐渐被多细胞球体所代替。此外，球状体的原位形成对于上调低氧适应性信号（例如，与OEG1水凝胶中的贴壁细胞相比，低氧诱导因子1α，HIF-1α可以增强血管生成因子（例如，血管内皮生长因子（VEGF）和成纤维细胞生长因子2（FGF-2））的分泌。与OEG1水凝胶中的贴壁细胞相比，与带有球体的低聚（乙二醇）400（OEG9）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。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。与OEG1水凝胶中的贴壁细胞相比，与带有球体的低聚（乙二醇）400（OEG9）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。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。与OEG1水凝胶中的贴壁细胞相比，与带有球体的低聚（乙二醇）400（OEG9）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。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。