State Key Laboratory of Solidification Processing, Center for Nano Energy Materials, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi'an, 710072, China.
Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, CA, 90095, USA.
Small. 2022 May;18(21):e2107714. doi: 10.1002/smll.202107714. Epub 2022 Apr 29.
Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) is combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers can be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibit enhanced growth, proliferation, vascular endothelial growth factor production, and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds can greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis-related immunofluorescence staining indicate SG7 scaffolds demonstrate enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.
丝素蛋白(SF)是一种很有前途的肌腱修复生物材料,但它相对较硬的机械性能和低细胞亲和力限制了其在再生医学中的应用。同时,基于明胶的聚合物在细胞附着和组织重塑方面具有优势,但机械强度不足以再生像肌腱这样的坚韧组织。考虑到这些方面,在本研究中,将明胶甲基丙烯酰(GelMA)与 SF 结合,制造出一种机械强度高且具有生物活性的纳米纤维支架(SG)。通过改变 SF 和 GelMA 的比例,可以灵活调节 SG 纳米纤维的机械性能。与 SF 纳米纤维相比,在最佳组成(SG7)的 SG 纤维上接种间充质干细胞(MSCs)后,MSCs 的生长、增殖、血管内皮生长因子产生和肌腱形成基因表达行为得到增强。MSCs 培养在 SG7 支架上的条件培养基可以极大地促进肌腱细胞的迁移和增殖。组织学分析和肌腱形成相关免疫荧光染色表明,与其他组相比,SG7 支架在体内肌腱组织再生方面表现出增强的效果。因此,SF 和 GelMA 混合纳米纤维的合理组合可能有助于改善治疗效果,并解决组织工程化支架用于肌腱再生的挑战。