A “Bridge-Building” Glycan Scaffold Mimicking Microbial Invasion for In Situ Endothelialization,Advanced Materials

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A “Bridge-Building” Glycan Scaffold Mimicking Microbial Invasion for In Situ Endothelialization
Advanced Materials ( IF 27.4 ) Pub Date : 2021-09-02 , DOI: 10.1002/adma.202103490
Ruoyu Mu ₁ , Yuhan Zhang ₁ , Lingli Yan ₁ , Zhencheng Liao ₁ , Yushun Yang ₂ , Huanxing Su ₁ , Lei Dong ₂ , Chunming Wang ₁

Affiliation

The globally high prevalence of peripheral artery diseases poses a pressing need for biomaterials grafts to rebuild vasculature. When implanted, they should promote endothelial cells (ECs) adhesion both profoundly and selectively—but the latter expectation remains unfulfilled. Here, this work is inspired by fungi that invade blood vessels via the “bridge” of galectins that, secreted by ECs, can simultaneously bind carbohydrates on fungal surface and integrin receptors on ECs. A glucomannan decanoate (GMDE) substrate mimicking fungal carbohydrates that highly and preferentially supports ECs adhesion while rejecting several other cell types is designed. Electrospun GMDE scaffolds efficiently sequester endogenous galectin-1—which bridges ECs to the scaffolds as it functions in fungal invasions—and promote blood perfusion in a murine limb ischemic model. Meanwhile, the application of GMDE requires no exogenous pro-angiogenic agents and causes no organ toxicity or adverse inflammation in mice, highlighting its high safety of potential translation. This glycan material, uniquely mimicking a microbial action and harnessing a secreted protein as a “bridge,” represents an effective, safe, and different strategy for ischemic vascular therapy.

中文翻译：

用于原位内皮化的“桥梁构建”聚糖支架模拟微生物入侵

全球外周动脉疾病的高发病率迫切需要生物材料移植物来重建脉管系统。植入后，它们应该能够深度和选择性地促进内皮细胞 (ECs) 的粘附——但后一种期望仍未实现。在这里，这项工作受到真菌的启发，真菌通过半乳凝素的“桥”侵入血管，半乳凝素由 EC 分泌，可以同时结合真菌表面的碳水化合物和 EC 上的整合素受体。设计了一种模仿真菌碳水化合物的葡甘露聚糖癸酸酯 (GMDE) 底物，该底物高度且优先支持 ECs 粘附，同时拒绝其他几种细胞类型。电纺 GMDE 支架有效隔离内源性 galectin-1——它在真菌侵袭中发挥作用，将 ECs 连接到支架上——并促进小鼠肢体缺血模型中的血液灌注。同时，GMDE的应用不需要外源性促血管生成剂，不会对小鼠造成器官毒性或不良炎症，突出了其潜在转化的高安全性。这种聚糖材料独特地模仿微生物作用并利用分泌的蛋白质作为“桥梁”，代表了一种有效、安全和不同的缺血性血管治疗策略。

更新日期：2021-10-20

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