Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208-3120, USA.
Biomaterials. 2012 Feb;33(5):1618-26. doi: 10.1016/j.biomaterials.2011.11.002. Epub 2011 Nov 29.
Therapeutic strategies following spinal cord injury must address the multiple barriers that limit regeneration. Multiple channel bridges have been developed that stabilize the injury following implantation and provide physical guidance for regenerating axons. These bridges have now been employed as a vehicle for localized delivery of lentivirus. Implantation of lentivirus loaded multiple channel bridges produced transgene expression that persisted for at least 4 weeks. Expression was maximal at the implant at the earliest time point, and decreased with increasing time of implantation, as well as rostral and caudal to the bridge. Immunohistochemical staining indicated transduction of macrophages, Schwann cells, fibroblasts, and astrocytes within the bridge and adjacent tissue. Subsequently, the delivery of lentivirus encoding the neurotrophic factors NT-3 or BDNF significantly increased the extent of axonal growth into the bridge relative to empty scaffolds. In addition to promoting axon growth, the induced expression of neurotrophic factors led to myelination of axons within the channels of the bridge, where the number of myelinated axons was significantly enhanced relative to control. Combining gene delivery with biomaterials to provide physical guidance and create a permissive environment can provide a platform to enhance axonal growth and promote regeneration.
脊髓损伤后的治疗策略必须解决限制再生的多种障碍。已经开发出了多种通道桥，这些桥在植入后稳定损伤，并为再生轴突提供物理指导。这些桥现在已被用作局部递送电病毒的载体。植入负载有慢病毒的多通道桥后，转导基因表达至少持续了 4 周。在最早的时间点，在植入物处的表达达到最大值，并且随着植入时间的增加以及桥的头端和尾端而降低。免疫组织化学染色表明在桥内和相邻组织中转导了巨噬细胞、施万细胞、成纤维细胞和星形胶质细胞。随后，慢病毒编码神经营养因子 NT-3 或 BDNF 的递送至桥内的轴突生长程度显著增加，与空支架相比。除了促进轴突生长外，诱导表达的神经营养因子还导致桥内通道中的轴突髓鞘形成，其中髓鞘化轴突的数量与对照相比显著增加。将基因传递与生物材料结合起来提供物理指导和创造允许的环境，可以提供一个增强轴突生长和促进再生的平台。
