Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Department of Stomatology, Zhejiang University School of Medicine, Hangzhou 310058, China.
J Zhejiang Univ Sci B. 2020;21(11):871-884. doi: 10.1631/jzus.B2000355.
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.
纳米纤维可以通过创造更适合细胞生长的环境来模拟天然组织结构，从而促使纳米纤维材料得到广泛应用。在这篇综述中，我们纳入了相关研究，并对纳米纤维对间充质干细胞的影响以及影响细胞黏附与成骨分化的因素进行了特征描述。我们假设体外骨再生过程类似于体内骨形成和愈合过程，并且纳米纤维或纳米纤维支架越接近天然骨组织，骨再生过程就越好。总的来说，在纳米纤维上培养的细胞与体外成骨补充剂诱导的细胞具有相似的基因表达模式和成骨行为。涉及细胞黏附（黏着斑激酶 (FAK)）、细胞骨架组织和成骨途径（转化生长因子-β (TGF-β)/骨形态发生蛋白 (BMP)、丝裂原活化蛋白激酶 (MAPK)和 Wnt）的基因被相继上调。细胞黏附和成骨可能受到多种因素的影响。纳米纤维具有某些物理特性，包括良好的亲水性、多孔性和溶胀性，这些特性促进了细胞的黏附和生长。此外，纳米纤维的硬度在细胞命运中起着至关重要的作用，因为对于更硬的支架，细胞募集用于成骨的效果更好，与整合素和 Yes 相关蛋白 (YAP)/含有 PDZ 结合基序的转录共激活因子 (TAZ)相关的信号通路也是如此。此外，层次排列的纳米纤维及其与功能添加剂（生长因子、HA 颗粒等）的结合，有助于成骨和骨再生。总之，先前的研究表明，当干细胞感知到纳米纤维环境的硬度及其它特性时，它们会相应地改变形状和张力，调节下游通路，随后黏附在纳米纤维上，从而有助于成骨。然而，还需要进行更多的实验来确定骨再生过程中的主要信号通路，并充分研究其在构建或设计最佳组织模拟纳米纤维支架方面的支持作用。
