Spatial-Controlled Coating of Pro-Angiogenic Proteins on 3D Porous Hydrogels Guides Endothelial Cell Behavior.

Spatial-Controlled Coating of Pro-Angiogenic Proteins on 3D Porous Hydrogels Guides Endothelial Cell Behavior.
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促血管生成蛋白在3D多孔水凝胶上的空间控制涂层指导内皮细胞行为。

DOI:
10.3390/ijms232314604
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发表时间:
2022-11-23
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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在组织工程中,细胞外基质(ECM)内分子成分的组成和结构排列决定了支架的物理和生化特征,从而调节细胞行为和功能。 ECM 的微环境在调节血管生成中发挥着重要作用。组织工程中的许多策略都试图通过使用简化的系统来控制模拟体内血管生成的空间线索。本研究的目的是开发具有不同空间呈现的促血管生成分子的 3D 多孔交联水凝胶,以指导内皮细胞 (EC) 行为。具有孔和预制微通道的水凝胶是用医药级普鲁兰多糖和葡聚糖制成的,并用新型促血管生成蛋白聚合物(Caf1-YIGSR 和 Caf1-VEGF)进行功能化。水凝胶功能化是通过掺入二乙氨基乙基(DEAE)-葡聚糖通过静电相互作用实现的。通过冷冻干燥和 Caf1 分子物理吸收相结合,实现了水凝胶的空间控制涂层。功能化支架中的细胞存活、粘附并增殖超过 7 天。当单独掺入时,Caf1-YIGSR 主要诱导细胞粘附和增殖,而 Caf1-VEGF 则促进细胞迁移和出芽。最重要的是,定向细胞迁移需要微通道和孔中同时存在两种蛋白质,这突出表明需要 Caf1-YIGSR 提供​​的粘附基质才能使 Caf1-VEGF 发挥作用。这项研究证明了通过促血管生成线索的空间控制来引导 EC 行为的能力,用于研究 3D 促血管生成信号并开发促血管生成可植入材料。
In tissue engineering, the composition and the structural arrangement of molecular components within the extracellular matrix (ECM) determine the physical and biochemical features of a scaffold, which consequently modulate cell behavior and function. The microenvironment of the ECM plays a fundamental role in regulating angiogenesis. Numerous strategies in tissue engineering have attempted to control the spatial cues mimicking in vivo angiogenesis by using simplified systems. The aim of this study was to develop 3D porous crosslinked hydrogels with different spatial presentation of pro-angiogenic molecules to guide endothelial cell (EC) behavior. Hydrogels with pores and preformed microchannels were made with pharmaceutical-grade pullulan and dextran and functionalized with novel pro-angiogenic protein polymers (Caf1-YIGSR and Caf1-VEGF). Hydrogel functionalization was achieved by electrostatic interactions via incorporation of diethylaminoethyl (DEAE)–dextran. Spatial-controlled coating of hydrogels was realized through a combination of freeze-drying and physical absorption with Caf1 molecules. Cells in functionalized scaffolds survived, adhered, and proliferated over seven days. When incorporated alone, Caf1-YIGSR mainly induced cell adhesion and proliferation, whereas Caf1-VEGF promoted cell migration and sprouting. Most importantly, directed cell migration required the presence of both proteins in the microchannel and in the pores, highlighting the need for an adhesive substrate provided by Caf1-YIGSR for Caf1-VEGF to be effective. This study demonstrates the ability to guide EC behavior through spatial control of pro-angiogenic cues for the study of pro-angiogenic signals in 3D and to develop pro-angiogenic implantable materials.
DOI: 10.1002/stem.2846
发表时间: 2018-09
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