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Engineering Microenvironment for Endogenous Neural Regeneration after Spinal Cord Injury by Reassembling Extracellular Matrix
ACS Applied Materials & Interfaces ( IF 9.5 ) Pub Date : 2020-04-02 , DOI: 10.1021/acsami.9b19638
Haiqian Liu 1 , Xiaoting Xu 1 , Yujie Tu 1 , Kaixin Chen 1 , Li Song 1 , Jingyan Zhai 1 , Shengfeng Chen 1 , Limin Rong 2 , Libing Zhou 1 , Wutian Wu 1 , Kwok-Fai So 1 , Seeram Ramakrishna 1, 2, 3 , Liumin He 1, 2
Affiliation  

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.

中文翻译:

重组细胞外基质的脊髓损伤后内源性神经再生的工程微环境

脊髓损伤(SCI)后形成充满液体的囊性腔是神经再生的主要障碍。在这项研究中,SCI后腔被功能性自组装肽(F-SAP)纳米纤维水凝胶与生长因子“鸡尾酒”耦合。通过仔细调整生长因子与肽纳米纤维之间的物理障碍以及电荷诱导的相互作用,可以实现生长因子的持续释放。这种工程微环境引发了轴突再生,这是通过追踪背柱中的下降途径和对病灶外再生轴突的免疫化学检测确定的。此外,彻底研究了严重SCI后内源性NSC(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,形成了与切断的皮质脊髓束相互连接的互连。强大的内源性神经发生本质上导致运动和电生理特性的恢复。总之,与生长因子偶联的F-SAP纳米纤维水凝胶阐明了通过局部重组细胞外基质引发内源性神经发生的治疗作用。
更新日期:2020-04-03
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