Jiang Tongmeng, Heng Shujun, Huang Xianyuan, Zheng Li, Kai Dan, Loh Xian Jun, Zhao Jinmin
J Biomed Nanotechnol. 2019 May 1;15(5):1005-1017. doi: 10.1166/jbn.2019.2748.
Scaffolds for stem cell-based therapy of cartilage defect require bioactivity and stiffness mimicking to the native cartilage matrix. In this study, we fabricated electrospun nanofibers composited of cartilage matrix components (collagen or chondroitin sulfate) and poly(ε-caprolactone)-polytetrahydrofuran (PCL-PTHF). PCL-PTHF with rat tail derived collagen was named PR and PCL-PTHF with chondroitin sulfate (PS) termed PS, which have a modulus of 7.5 MPa and 3.6 MPa, respectively, within the range of cartilage matrix. Their chondrogenic potential for guiding chondrogenic differentiation and promoting cartilage regeneration were investigated based upon mesenchymal stem cells (MSCs). Results showed that both PR and PS nanofibers have the ability to induce chondrogenesis of MSCs and accelerate the regeneration of injured cartilage surface, probably via the suppression of Tumor necrosis factor (TNF) signaling pathway as evidenced by microarray profiles. Comparatively, PR showed better chondrogenic potential both and than that of PS, which may induce chondrogenesis through Hypoxia inducing factor-1 (HIF-1) signaling pathway. This study may provide reference for MSC based therapy of cartilage defects.
用于基于干细胞的软骨缺损治疗的支架需要具有与天然软骨基质相似的生物活性和硬度。在本研究中,我们制备了由软骨基质成分(胶原蛋白或硫酸软骨素)与聚(ε-己内酯)-聚四氢呋喃(PCL-PTHF)复合而成的电纺纳米纤维。含大鼠尾源胶原蛋白的PCL-PTHF称为PR,含硫酸软骨素的PCL-PTHF称为PS,它们的模量分别为7.5 MPa和3.6 MPa,在软骨基质范围内。基于间充质干细胞(MSCs)研究了它们在引导软骨生成分化和促进软骨再生方面的软骨生成潜力。结果表明,PR和PS纳米纤维都具有诱导MSCs软骨生成和加速损伤软骨表面再生的能力,可能是通过抑制肿瘤坏死因子(TNF)信号通路,这在微阵列分析中得到了证实。相比之下,PR在体内和体外都显示出比PS更好的软骨生成潜力,PS可能通过缺氧诱导因子-1(HIF-1)信号通路诱导软骨生成。本研究可为基于MSCs的软骨缺损治疗提供参考。