MOE Joint International Research Laboratory of CNS Regeneration, Guangdong-Hong Kong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou 510632, China.
Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
ACS Appl Mater Interfaces. 2020 Apr 15;12(15):17207-17219. doi: 10.1021/acsami.9b19638. Epub 2020 Apr 2.
The formation of a fluid-filled cystic cavity after spinal cord injury (SCI) is a major obstacle for neural regeneration. In this study, the post-SCI cavity was bridged by a functional self-assembling peptide (F-SAP) nanofiber hydrogel coupled with growth factor "cocktail". A sustained release of growth factors was achieved by carefully tailoring the physical hindrances and charge-induced interactions between the growth factors and the peptide nanofibers. Such an engineering microenvironment elicited axon regeneration, as determined by tracing of the descending pathway in the dorsal columns and immunochemical detection of regenerating axons beyond the lesion. Furthermore, the dynamic spatiotemporal activation line of endogenous NSCs (eNSCs) after severe SCI was thoroughly investigated. The results indicated that the growth factor-coupled F-SAP greatly facilitated eNSC proliferation, neuronal differentiation, maturation, myelination, and more importantly, the formation of interconnection with severed descending corticospinal tracts. The robust endogenous neurogenesis essentially led to the recovery of locomotion and electrophysiological properties. In conclusion, the growth factor-coupled F-SAP nanofiber hydrogel elucidated the therapeutic effect of eliciting endogenous neurogenesis by locally reassembling an extracellular matrix.
脊髓损伤（SCI）后形成充满液体的囊腔是神经再生的主要障碍。在这项研究中，通过功能自组装肽（F-SAP）纳米纤维水凝胶与生长因子“鸡尾酒”桥接 SCI 后的囊腔。通过精心调整生长因子与肽纳米纤维之间的物理障碍和电荷诱导相互作用，实现了生长因子的持续释放。这种工程微环境引发了轴突再生，这可以通过追踪背柱中的下行途径和免疫化学检测损伤部位以外的再生轴突来确定。此外，还彻底研究了严重 SCI 后内源性神经干细胞（eNSC）的动态时空激活线。结果表明，生长因子偶联的 F-SAP 极大地促进了 eNSC 的增殖、神经元分化、成熟、髓鞘形成，更重要的是，与切断的皮质脊髓束形成了连接。强大的内源性神经发生本质上导致了运动和电生理特性的恢复。总之，生长因子偶联的 F-SAP 纳米纤维水凝胶通过局部重新组装细胞外基质阐明了诱导内源性神经发生的治疗效果。
