多孔支架-水凝胶复合材料空间调节三维细胞力学传感

IF 2.7 Q3 ENGINEERING, BIOMEDICAL Frontiers in medical technology Pub Date : 2022-05-02 DOI:10.3389/fmedt.2022.884314
M. DiCerbo, M. M. Benmassaoud, Sebastián L. Vega
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引用次数: 2

摘要

被包裹在三维水凝胶中的细胞表现出不同的细胞力学感知能力,这是基于它们重塑周围水凝胶环境的能力。尽管组织界面中的细胞具有一系列机械敏感状态,但在3D生物材料中重建这一状态具有挑战性。包裹在甲基丙烯酸明胶(GelMe)水凝胶中的人间充质干细胞(MSCs)以一种时间依赖性的方式重塑其局部水凝胶环境,在培养3至5天期间,细胞体积和细胞核yes相关蛋白(YAP)定位显著增加。压缩有限元分析模型显示了压缩GelMe水凝胶的水凝胶应力的空间差异,并将msc负载的GelMe水凝胶压缩(0-50%)3天,以评估水凝胶应力的空间差异对三维细胞力学传感的作用。与25%压缩GelMe水凝胶的中心(低应力)MSCs相比,边缘(高应力)MSCs明显更大,更少圆形,并且核YAP增加。在50%的压缩下,GelMe水凝胶始终处于高应力状态,这导致整个水凝胶中MSC体积和核YAP的持续增加。为了重现存在于组织界面中的异质机械信号,我们将载msc的凝胶溶液灌注到多孔聚己内酯(PCL)支架中。不同孔径(~280 ~ 430 μm)构建的MSCs,随着孔径的增大,形貌和细胞核YAP的变化幅度增大。水凝胶应力影响间充质干细胞的力学传感,多孔支架-水凝胶复合材料使间充质干细胞暴露于不同的机械信号中,是研究和设计组织界面的独特生物材料。
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Porous Scaffold-Hydrogel Composites Spatially Regulate 3D Cellular Mechanosensing
Cells encapsulated in 3D hydrogels exhibit differences in cellular mechanosensing based on their ability to remodel their surrounding hydrogel environment. Although cells in tissue interfaces feature a range of mechanosensitive states, it is challenging to recreate this in 3D biomaterials. Human mesenchymal stem cells (MSCs) encapsulated in methacrylated gelatin (GelMe) hydrogels remodel their local hydrogel environment in a time-dependent manner, with a significant increase in cell volume and nuclear Yes-associated protein (YAP) localization between 3 and 5 days in culture. A finite element analysis model of compression showed spatial differences in hydrogel stress of compressed GelMe hydrogels, and MSC-laden GelMe hydrogels were compressed (0–50%) for 3 days to evaluate the role of spatial differences in hydrogel stress on 3D cellular mechanosensing. MSCs in the edge (high stress) were significantly larger, less round, and had increased nuclear YAP in comparison to MSCs in the center (low stress) of 25% compressed GelMe hydrogels. At 50% compression, GelMe hydrogels were under high stress throughout, and this resulted in a consistent increase in MSC volume and nuclear YAP across the entire hydrogel. To recreate heterogeneous mechanical signals present in tissue interfaces, porous polycaprolactone (PCL) scaffolds were perfused with an MSC-laden GelMe hydrogel solution. MSCs in different pore diameter (~280–430 μm) constructs showed an increased range in morphology and nuclear YAP with increasing pore size. Hydrogel stress influences MSC mechanosensing, and porous scaffold-hydrogel composites that expose MSCs to diverse mechanical signals are a unique biomaterial for studying and designing tissue interfaces.
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CiteScore
3.70
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审稿时长
13 weeks
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