纳米纤维对间充质干细胞的影响:影响细胞粘附和成骨分化的环境因素及其机理

Effects of nanofibers on mesenchymal stem cells:environmental factors affecting cell adhesion and osteogenic differentiation and their mechanisms

纳米纤维可以建造适合细胞生长的环境,这种仿生性能促进了纳米纤维材料的广泛应用。在这篇综述中,我们检索了相关研究,并归纳总结了纳米纤维对间充质干细胞的影响,以及影响细胞粘附和成骨分化的因素。我们假设:体外的骨再生过程与体内骨形成和愈合的过程类似;纳米纤维或其支架材料与天然骨组织越接近,骨再生过程就越好。通常,在纳米纤维上培养的细胞具有与体外成骨诱导下的细胞相似的基因表达模式和成骨分化。在此过程中,诸多基因通路表达相继上调(例如,与细胞粘附有关的基因FAK(黏着斑激酶)、与细胞骨架变化和成骨分化有关的基因通路转化生长因子-β(TGF-β)/骨形态发生蛋白(BMP)、促分裂原活化蛋白激酶(MAPK)和Wnt等)。细胞粘附和成骨分化可能受到多种因素的影响。纳米纤维的某些物理性质能够促进细胞粘附和生长,包括合适的亲水性、孔隙率和溶胀性。此外,纳米纤维的硬度在细胞命运中起着至关重要的作用,在较坚硬的支架上,成骨细胞的募集往往更好,其中整合素和YAP/TAZ信号通路与之密切相关。同时,纳米纤维的分层排列结构以及它们与功能性添加剂(生长因子、羟基磷灰石颗粒等)的组合也有助于成骨和骨再生。总而言之,在检测到纳米纤维环境的硬度及其他特征后,干细胞会相应地改变其形状和张力,调节下游路径,接着粘附至纳米纤维并开始成骨分化。然而,成骨分化过程中的主要信号通路还需要更多实验证实,从而为设计及制作最理想的仿生纳米纤维支架提供理论支持。

Nanofibers can mimic natural tissue structure by creating a more suitable environment for cells to grow,prompting a wide application of nanofiber materials.In this review,we include relevant studies and characterize the effect of nanofibers on mesenchymal stem cells,as well as factors that affect cell adhesion and osteogenic differentiation.We hypothesize that the process of bone regeneration in vitro is similar to bone formation and healing in vivo,and the closer nanofibers or nanofibrous scaffolds are to natural bone tissue,the better the bone regeneration process will be.In general,cells cultured on nanofibers have a similar gene expression pattern and osteogenic behavior as cells induced by osteogenic supplements in vitro.Genes involved in cell adhesion(focal adhesion kinase(FAK)),cytoskeletal organization,and osteogenic pathways(transforming growth factor-β(TGF-β)/bone morphogenic protein(BMP),mitogen-activated protein kinase(MAPK),and Wnt)are upregulated successively.Cell adhesion and osteogenesis may be influenced by several factors.Nanofibers possess certain physical properties including favorable hydrophilicity,porosity,and swelling properties that promote cell adhesion and growth.Moreover,nanofiber stiffness plays a vital role in cell fate,as cell recruitment for osteogenesis tends to be better on stiffer scaffolds,with associated signaling pathways of integrin and Yes-associated protein(YAP)/transcriptional co-activator with PDZ-binding motif(TAZ).Also,hierarchically aligned nanofibers,as well as their combination with functional additives(growth factors,HA particles,etc.),contribute to osteogenesis and bone regeneration.In summary,previous studies have indicated that upon sensing the stiffness of the nanofibrous environment as well as its other characteristics,stem cells change their shape and tension accordingly,regulating downstream pathways followed by adhesion to nanofibers to contribute to osteogenesis.However,additional experiments are needed to identify major signaling pathways in the bone regeneration process,and also to fully investigate its supportive role in fabricating or designing the optimum tissue-mimicking nanofibrous scaffolds.