DiCerbo Matthew, Benmassaoud Mohammed Mehdi, Vega Sebastián L
Department of Biomedical Engineering, Rowan University, Glassboro, NJ, United States.
Front Med Technol. 2022 May 2;4:884314. doi: 10.3389/fmedt.2022.884314. eCollection 2022.
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.
封装在三维水凝胶中的细胞，根据其重塑周围水凝胶环境的能力，在细胞机械传感方面表现出差异。尽管组织界面中的细胞具有一系列机械敏感状态，但在三维生物材料中重现这一现象具有挑战性。封装在甲基丙烯酸化明胶（GelMe）水凝胶中的人间充质干细胞（MSCs）以时间依赖性方式重塑其局部水凝胶环境，培养3至5天时细胞体积和细胞核Yes相关蛋白（YAP）定位显著增加。压缩的有限元分析模型显示了压缩GelMe水凝胶的水凝胶应力存在空间差异，将负载MSC的GelMe水凝胶压缩（0 - 50%）3天，以评估水凝胶应力空间差异对三维细胞机械传感的作用。与25%压缩GelMe水凝胶中心（低应力）的MSCs相比，边缘（高应力）的MSCs明显更大、更不圆，且细胞核YAP增加。在50%压缩时，GelMe水凝胶整体处于高应力状态，这导致整个水凝胶中MSC体积和细胞核YAP持续增加。为了重现组织界面中存在的异质机械信号，用负载MSC的GelMe水凝胶溶液灌注多孔聚己内酯（PCL）支架。不同孔径（约280 - 430μm）构建体中的MSCs随着孔径增加，形态和细胞核YAP的变化范围增大。水凝胶应力影响MSC机械传感，使MSCs暴露于不同机械信号的多孔支架 - 水凝胶复合材料是研究和设计组织界面的独特生物材料。
