Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Biomaterials. 2013 Jul;34(22):5571-80. doi: 10.1016/j.biomaterials.2013.04.004. Epub 2013 Apr 24.
Electrospinning has recently gained much interest due to its ability to form scaffolds that mimic the nanofibrous nature of the extracellular matrix, such as the size and depth-dependent alignment of collagen fibers within hyaline cartilage. While much progress has been made in developing bulk, isotropic hydrogels for tissue engineering and understanding how the microenvironment of such scaffolds affects cell response, these effects have not been extensively studied in a nanofibrous system. Here, we show that the mechanics (through intrafiber crosslink density) and adhesivity (through RGD density) of electrospun hyaluronic acid (HA) fibers significantly affect human mesenchymal stem cell (hMSC) interactions and gene expression. Specifically, hMSC spreading, proliferation, and focal adhesion formation were dependent on RGD density, but not on the range of fiber mechanics investigated. Moreover, traction-mediated fiber displacements generally increased with more adhesive fibers. The expression of chondrogenic markers, unlike trends in cell spreading and cytoskeletal organization, was influenced by both fiber mechanics and adhesivity, in which softer fibers and lower RGD densities generally enhanced chondrogenesis. This work not only reveals concurrent effects of mechanics and adhesivity in a fibrous context, but also highlights fibrous HA hydrogels as a promising scaffold for future cartilage repair strategies.
静电纺丝技术因其能够形成模仿细胞外基质纳米纤维特性的支架而受到广泛关注，例如透明软骨中胶原纤维的大小和深度依赖性排列。虽然在开发用于组织工程的块状各向同性水凝胶以及理解此类支架的微环境如何影响细胞反应方面已经取得了很大进展，但在纳米纤维系统中尚未广泛研究这些影响。在这里，我们表明静电纺丝透明质酸（HA）纤维的力学性质（通过纤维内交联密度）和粘附性（通过 RGD 密度）显著影响人间充质干细胞（hMSC）的相互作用和基因表达。具体而言，hMSC 的铺展、增殖和焦点粘附形成取决于 RGD 密度，但与所研究的纤维力学范围无关。此外，牵引力介导的纤维位移通常随着更具粘附性的纤维而增加。与细胞铺展和细胞骨架组织的趋势不同，软骨生成标志物的表达受到纤维力学和粘附性的共同影响，其中较软的纤维和较低的 RGD 密度通常会增强软骨生成。这项工作不仅揭示了纤维环境中力学和粘附性的并发影响，还强调了纤维状 HA 水凝胶作为未来软骨修复策略的有前途的支架。
