Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
Biomaterials. 2010 Mar;31(8):2323-34. doi: 10.1016/j.biomaterials.2009.11.073. Epub 2009 Dec 8.
Artificial nerve conduits (NC) can be used as an alternative to autologous nerve grafts to enhance the repair of small nerve gaps. Current NC lack adequate molecular and structural functionalities. Thus, we developed silk fibroin NC (SF NC) that were loaded with glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) and topographically functionalized with aligned and non-aligned SF nanofibers. The SF NC were produced from fully functionalized SF membranes on which initial experiments were performed. DRG (dorsal root ganglions) sensory neurons and spinal cord (SpC) motor neurons, both from chicken embryos, exhibited an augmented length and rate of axonal outgrowth parallel to the aligned nanofibers. In addition, glial cells from DRG proliferated and migrated in close association and even slightly ahead of the outgrowing axons. On the contrary, axonal and glial growth was slower and randomly oriented on non-aligned nanofibers. The DRG and SpC explants were also inserted into the lumen of the finished SF NC. The unidirectional orientation of axo-glial outgrowth from the explants evidenced the preservation of the trophic and topographical functionalities in the SF NC. Bioactive GDNF and NGF were released in vitro from SF NC over 4 weeks. Thus, the developed functionalized SF NC hold promise to enhance functional recovery of injured peripheral nerves.
人工神经导管（NC）可作为自体神经移植物的替代品，以增强小神经间隙的修复。目前的 NC 缺乏足够的分子和结构功能。因此，我们开发了丝素蛋白 NC（SF NC），它负载胶质细胞源性神经营养因子（GDNF）和神经生长因子（NGF），并在拓扑结构上用对齐和非对齐的 SF 纳米纤维进行功能化。SF NC 是由最初在其上进行实验的完全功能化 SF 膜产生的。鸡胚的背根神经节（DRG）感觉神经元和脊髓（SpC）运动神经元都表现出与对齐的纳米纤维平行的轴突生长的长度和速率增加。此外，来自 DRG 的神经胶质细胞增殖并紧密地与生长的轴突一起迁移，甚至略微领先于生长的轴突。相反，在非对齐的纳米纤维上，轴突和神经胶质的生长较慢且方向随机。DRG 和 SpC 外植体也被插入到 SF NC 的管腔中。来自外植体的轴突-神经胶质生长的单向取向证明了 SF NC 中保留了营养和拓扑功能。在体外，生物活性 GDNF 和 NGF 从 SF NC 中释放出来超过 4 周。因此，开发的功能化 SF NC 有望增强受损周围神经的功能恢复。
