Macroporous Hydrogels Upregulate Osteogenic Signal Expression and Promote Bone Regeneration
Macroporous Hydrogels Upregulate Osteogenic Signal Expression and Promote Bone Regeneration
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DOI：
10.1021/bm100061z
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发表时间：
2010-05-01
影响因子：
6.2
通讯作者：
Fisher, John P.
中科院分区：
文献类型：
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作者：
Betz, Martha W.;Yeatts, Andrew B.;Fisher, John P.
本研究旨在探讨大孔水凝胶结构对人骨髓间充质干细胞（hMSCs）成骨信号表达和分化的影响。特别是，我们提出了一种用于眼眶骨修复的组织工程方法，该方法基于由5-乙基-5-（羟甲基）-β，β-二甲基-1，3-二氧六环-2-乙醇二丙烯酸酯（EHD）和聚（乙二醇）二丙烯酸酯（PEGDA）形成的环状缩醛生物材料。El-ID单体和PEGDA聚合物可以通过自由基聚合和随后的致孔剂浸出（一种用于亲水性凝胶的新技术）制成大孔水凝胶。我们假设EH-PEG水凝胶的大孔性促进了hMSCs之间的细胞间信号传导。为了研究这种现象，将hMSC装载到具有不同孔径和孔隙率的El-I-PEG水凝胶中。检测hMSCs的存活率、hMSCs表达骨形态发生蛋白-2（BMP-2）、BMP受体1A型和BMP受体2型以及hMSCs的分化情况。结果表明，大孔El-I-PEG水凝胶支持hMSC，并且这种大孔环境促进hMSC的BMP-2表达的显著增加。这种BMP-2表达的上调与更快速的hMSC分化相关，如通过碱性磷酸酶表达所测量的。通过加入纤连蛋白改变hMSC与EH-PEG水凝胶表面的相互作用，似乎没有增加BMP-2的表达。因此，我们推测，EH-PEG水凝胶大孔有利于自分泌和旁分泌信号通过定位内源性表达的因子在水凝胶的孔，从而促进hMSC成骨细胞分化和骨再生。
The objective of this work was to investigate the effects of macroporous hydrogel architecture on the osteogenic signal expression and differentiation of human mesenchymal stem cells (hMSCs). In particular, we have proposed a tissue engineering approach for orbital bone repair based on a cyclic acetal biomaterial formed from 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). The El-ID monomer and PEGDA polymer may be fabricated into macroporous hydrogels by radical polymerization and subsequent porogen leaching, a novel technique for hydrophilic gels. We hypothesized that EH-PEG hydrogel macroporosity facilitates intercellular signaling among hMSCs. To investigate this phenomenon, hMSCs were loaded into El-I-PEG hydrogels with varying pore size and porosity. The viability of hMSCs, the expression of bone morphogenetic protein-2 (BMP-2), BMP receptor type 1A, and BMP receptor type 2 by hMSCs, and the differentiation of hMSCs were then assessed. Results demonstrate that macroporous El-I-PEG hydrogels support hMSCs and that this macroporous environment promotes a dramatic increase in BMP-2 expression by hMSCs. This upregulation of BMP-2 expression is associated by a more rapid hMSC differentiation, as measured by alkaline phosphatase expression. Altering hMSC interactions with the EH-PEG hydrogel surface, by the addition of fibronectin, did not appear to augment BMP-2 expression. We therefore speculate that EH-PEG hydrogel macroporosity facilitates autocrine and paracrine signaling by localizing endogenously expressed factors within the hydrogel's pores and thus promotes hMSC osteoblastic differentiation and bone regeneration.