Key Laboratory of Neuroregeneration, Ministry of Education and Jiangsu Province, Co-innovation Center of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong 226001, PR China.
Key Laboratory of Neuroregeneration, Ministry of Education and Jiangsu Province, Co-innovation Center of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong 226001, PR China; Medical School of Nantong University, Nantong University, Nantong 226001, PR China.
Mater Sci Eng C Mater Biol Appl. 2022 Apr;135:112674. doi: 10.1016/j.msec.2022.112674. Epub 2022 Jan 22.
Successful repair and desirable functional recovery of large-gap nerve injuries using artificial nerve implants remains a significant clinical challenge. The beneficial bionic microenvironment within scaffolds can significantly promote the outgrowth of newborn nerve tissues after implantation. Herein, we developed an aligned silk-inspired fiber scaffold (RGD@ASFFs) with a synergistic effect of an extracellular matrix mimicking physical cues and RGD (Arg-Gly-Asp) signals to provide an enhanced cell-friendly microenvironment for repairing large-gap peripheral nerve injuries. The topographic alignment of the methacrylated silk fibroin electrospun fibers effectively facilitated axonal guidance and oriented Schwann cell growth. Importantly, the mechanical cue combined with cell adhesion signals provided by RGD peptides further triggered enriched myelination of Schwann cells by nuclear translocation of Yes-associated protein 1 (YAP) to secrete neurotrophins to support axonal growth. Moreover, benefiting from improved neuronal extension and re-myelination, promising motor function recovery in vivo was achieved by RGD@ASFFs, which is comparable to that of autografts. Thus, the design of this engineered bionic scaffold is a powerful strategy for peripheral nerve defect repair.
利用人工神经植入物成功修复和理想的功能恢复大间隙神经损伤仍然是一个重大的临床挑战。支架内有益的仿生微环境可以显著促进植入后新生神经组织的生长。在此，我们开发了一种具有协同作用的取向丝素启发纤维支架（RGD@ASFFs），该支架模拟了细胞外基质的物理线索和 RGD（精氨酸-甘氨酸-天冬氨酸）信号，为修复大间隙周围神经损伤提供了增强的细胞友好微环境。甲基丙烯酰化丝素静电纺纤维的形貌取向有效地促进了轴突导向和雪旺细胞的定向生长。重要的是，机械线索和 RGD 肽提供的细胞黏附信号进一步触发了富含髓鞘的雪旺细胞，通过 Yes 相关蛋白 1（YAP）的核转位分泌神经营养因子来支持轴突生长。此外，得益于神经元延伸和再髓鞘化的改善，RGD@ASFFs 实现了有希望的体内运动功能恢复，可与自体移植物相媲美。因此，这种工程仿生支架的设计是修复周围神经缺损的一种有力策略。
