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首页> 外文期刊>Acta biomaterialia >Differential effect of hypoxia on human mesenchymal stem cell chondrogenesis and hypertrophy in hyaluronic acid hydrogels
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Differential effect of hypoxia on human mesenchymal stem cell chondrogenesis and hypertrophy in hyaluronic acid hydrogels

机译：低氧对透明质酸水凝胶对人间充质干细胞软骨形成和肥大的影响

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摘要

Photocrosslinked hyaluronic acid (HA) hydrogels provide a conducive 3-D environment that supports the chondrogenesis of human mesenchymal stem cells (hMSCs). The HA macromer concentration in the hydrogels has a significant impact on the chondrogenesis of the encapsulated MSCs due to changes in the physical properties of the hydrogels. Meanwhile, hypoxia has been shown to promote MSC chondrogenesis and suppress subsequent hypertrophy. This study investigates the combinatorial effect of tuning HA macromer concentration (1.5-5% w/v) and hypoxia on MSC chondrogenesis and hypertrophy. To decouple the effect of HA concentration from that of crosslinking density, the HA hydrogel crosslinking density was adjusted by varying the extent of the reaction through the light exposure time while keeping the HA concentration constant (5% w/v at 5 or 15 min). It was found that hypoxia had no significant effect on the chondrogenesis and cartilaginous matrix synthesis of hMSCs under all hydrogel conditions. In contrast, the hypoxia-mediated positive or negative regulation of hMSC hypertrophy in HA hydrogels is dependent on the HA concentration but independent of the crosslinking density. Specifically, hypoxia significantly suppressed hMSC hypertrophy and neocartilage calcification in low HA concentration hydrogels, whereas hypoxia substantially enhanced hMSC hypertrophy, leading to elevated tissue calcification in high HA concentration hydrogels irrespective of their crosslinking density. In addition, at a constant high HA concentration, increasing hydrogel crosslinking density promoted hMSC hypertrophy and matrix calcification. To conclude, the findings from this study demonstrate that the effect of hypoxia on hMSC chondrogenesis and hypertrophy is differentially influenced by the encapsulating HA hydrogel properties.
机译：光交联的透明质酸（HA）水凝胶提供了有利的3-D环境，可支持人间充质干细胞（hMSCs）的软骨形成。由于水凝胶物理性质的变化，水凝胶中HA大分子单体的浓度对封装的MSC的软骨形成有重大影响。同时，低氧已被证明可促进MSC软骨形成并抑制随后的肥大。这项研究调查调整HA大单体浓度（1.5-5％w / v）和缺氧对MSC软骨形成和肥大的组合作用。为了使HA浓度的影响与交联密度的影响脱钩，在保持HA浓度恒定（5％w / v在5或15分钟）的情况下，通过改变曝光时间改变反应程度来调节HA水凝胶的交联密度。 。发现在所有水凝胶条件下，缺氧对hMSCs的软骨形成和软骨基质合成没有显着影响。相反，HA水凝胶中缺氧介导的hMSC肥大的正向或负向调节取决于HA浓度，但不依赖于交联密度。具体而言，低氧显着抑制了低HA浓度水凝胶中的hMSC肥大和新软骨钙化，而低氧显着增强了hMSC肥大，从而导致高HA浓度水凝胶中的组织钙化升高，无论其交联密度如何。此外，在恒定的高HA浓度下，水凝胶交联密度的增加促进了hMSC肥大和基质钙化。总而言之，这项研究的结果表明低氧对hMSC软骨形成和肥大的影响受封装HA水凝胶特性的影响不同。

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