神经导管是一种很有前途的治疗长间隙周围神经损伤,然而它的功效是有限的。可释放药物的支架可以提供可靠的平台来构建用于神经恢复的再生微环境。在这项研究中,通过用于促进神经再生的连续3D打印技术制造封装有前药纳米组件的弹性水凝胶导管。生物活性水凝胶由明胶甲基丙烯酰基(GelMA)和丝素蛋白甲基丙烯酸缩水甘油酯(SF-MA)组成,对附着力表现出积极的影响,扩散,和施万细胞的迁移。同时,具有高载药能力的7,8-二羟基黄酮(7,8-DHF)前药纳米组装体通过亲脂性前药的自组装来开发并加载到GelMA/SF-MA水凝胶中。载药导管可持续释放7,8-DHF以促进神经突伸长。通过手术缝合大鼠坐骨神经,建立了12mm神经缺损模型,用于评估治疗效果。电生理学,形态学,组织学评估表明,该导管可以促进轴突再生,髓鞘再生,和功能恢复通过提供一个有利的微环境。这些发现暗示具有7,8-DHF释放的GelMA/SF-MA导管在治疗长间隙周围神经损伤方面具有潜力。
Nerve guide conduit is a promising treatment for long gap peripheral nerve injuries, yet its efficacy is limited. Drug-releasable scaffolds may provide reliable platforms to build a regenerative microenvironment for nerve recovery. In this study, an elastic hydrogel conduit encapsulating with prodrug nanoassemblies is fabricated by a continuous 3D printing technique for promoting nerve regeneration. The bioactive hydrogel is comprised of gelatin methacryloyl (GelMA) and silk fibroin glycidyl methacrylate (SF-MA), exhibiting positive effects on adhesion, proliferation, and migration of Schwann cells. Meanwhile, 7,8-dihydroxyflavone (7,8-DHF) prodrug nanoassemblies with high drug-loading capacities are developed through self-assembly of the lipophilic prodrug and loaded into the GelMA/SF-MA hydrogel. The drug loading conduit could sustainedly release 7,8-DHF to facilitate neurite elongation. A 12 mm nerve defect model is established for therapeutic efficiency evaluation by implanting the conduit through surgical suturing with rat sciatic nerve. The electrophysiological, morphological, and histological assessments indicate that this conduit can promote axon regeneration, remyelination, and function recovery by providing a favorable microenvironment. These findings implicate that the GelMA/SF-MA conduit with 7,8-DHF release has potentials in the treatment of long-gap peripheral nerve injury.