National University of Singapore, Singapore.
Differentiation. 2010 Feb;79(2):102-10. doi: 10.1016/j.diff.2009.11.001. Epub 2009 Dec 5.
Mesenchymal stem cells and precursor cells are ideal candidates for tendon and ligament tissue engineering; however, for the stem cell-based approach to succeed, these cells would be required to proliferate and differentiate into tendon/ligament fibroblasts on the tissue engineering scaffold. Among the various fiber-based scaffolds that have been used in tendon/ligament tissue engineering, hybrid fibrous scaffolds comprising both microfibers and nanofibers have been recently shown to be particularly promising. With the nanofibrous coating presenting a biomimetic surface, the scaffolds can also potentially mimic the natural extracellular matrix in function by acting as a depot for sustained release of growth factors. In this study, we demonstrate that basic fibroblast growth factor (bFGF) could be successfully incorporated, randomly dispersed within blend-electrospun nanofibers and released in a bioactive form over 1 week. The released bioactive bFGF activated tyrosine phosphorylation signaling within seeded BMSCs. The bFGF-releasing nanofibrous scaffolds facilitated BMSC proliferation, upregulated gene expression of tendon/ligament-specific ECM proteins, increased production and deposition of collagen and tenascin-C, reduced multipotency of the BMSCs and induced tendon/ligament-like fibroblastic differentiation, indicating their potential in tendon/ligament tissue engineering applications.
间充质干细胞和前体细胞是肌腱和韧带组织工程的理想候选者;然而,为了使基于干细胞的方法取得成功,这些细胞需要在组织工程支架上增殖并分化为肌腱/韧带成纤维细胞。在已经用于肌腱/韧带组织工程的各种纤维支架中,最近已经证明由微纤维和纳米纤维组成的混合纤维支架特别有前途。由于纳米纤维涂层呈现出仿生表面,因此支架还可以通过作为生长因子持续释放的储存库来模拟天然细胞外基质的功能。在这项研究中,我们证明了碱性成纤维细胞生长因子 (bFGF) 可以成功地掺入,随机分散在共混电纺纳米纤维中,并在 1 周内以生物活性形式释放。释放的生物活性 bFGF 在接种的 BMSCs 内激活酪氨酸磷酸化信号转导。释放 bFGF 的纳米纤维支架促进 BMSC 增殖,上调肌腱/韧带特异性细胞外基质蛋白的基因表达,增加胶原蛋白和腱糖蛋白-C 的产生和沉积,降低 BMSCs 的多能性并诱导肌腱/韧带样成纤维细胞分化,表明它们在肌腱/韧带组织工程应用中的潜力。
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