Aligned fibrin/functionalized self-assembling peptide interpenetrating nanofiber hydrogel presenting multi-cues promotes peripheral nerve functional recovery.

Aligned fibrin/functionalized self-assembling peptide interpenetrating nanofiber hydrogel presenting multi-cues promotes peripheral nerve functional recovery.
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对齐纤维蛋白/功能化自组装肽互穿纳米纤维水凝胶呈现多信号促进周围神经功能恢复

DOI:
10.1016/j.bioactmat.2021.05.056
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发表时间:
2022-03
影响因子:
18.9
通讯作者:
Wang X
Wang X
中科院分区:
工程技术1区
文献类型:
--
作者:
Yang S;Zhu J;Lu C;Chai Y;Cao Z;Lu J;Zhang Z;Zhao H;Huang YY;Yao S;Kong X;Zhang P;Wang X

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具有中空管腔的神经引导导管不能再生临界大小的周围神经缺损(大鼠15mm,人25mm),这可以通过有益的腔内微环境来改善。然而,腔内填充材料提供的个体线索不足以消除再生神经与正常神经之间的功能差距。本文通过静电纺丝和分子自组装构建了一种定向纤维蛋白/功能化自组装肽(AFG/fSAP)互穿纳米纤维水凝胶,该水凝胶可以为周围神经再生提供协同的地形和生化线索。该水凝胶具有排列结构、高含水量、合适的力学性能和适合神经修复的生物降解能力,在体外增强了原代雪旺细胞(SCs)的排列和神经营养因子的分泌,并在体内成功地桥接了大鼠15mm的坐骨神经间隙。大鼠移植AFG/fSAP水凝胶后,有髓神经纤维和神经支配肌肉的形态和功能恢复良好。AFG/fSAP水凝胶促进的运动功能恢复与自体移植物相当。此外,AFG/fSAP水凝胶上调再生相关基因的表达,激活再生神经中PI3K/Akt和MAPK信号通路。总之,AFG/fSAP水凝胶通过结构引导和生化刺激的结合,代表了周围神经修复的一种有前景的方法。首次构建了一种用于周围神经再生的新型排列互穿纳米纤维水凝胶。对齐的水凝胶为周围神经再生提供了协同的地形和生化线索。经定向水凝胶填充的神经导管可在12周内修复远端坐骨神经缺损。定向水凝胶促进的功能恢复与自体移植物相当。排列的水凝胶上调再生相关基因,激活PI3K/Akt和MAPK信号通路。
Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects (15 mm in rats and 25 mm in humans), which can be improved by a beneficial intraluminal microenvironment. However, individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal nerves. Herein, an aligned fibrin/functionalized self-assembling peptide (AFG/fSAP) interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular self-assembly. The hydrogel possesses an aligned structure, high water content, appropriate mechanical properties and suitable biodegradation capabilities for nerve repair, which enhances the alignment and neurotrophin secretion of primary Schwann cells (SCs) in vitro, and successfully bridges a 15-mm sciatic nerve gap in rats in vivo. The rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated muscles. The motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of autografts. Moreover, the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated nerve. Altogether, the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation. A novel aligned interpenetrating nanofiber hydrogel is first constructed for peripheral nerve regeneration. The aligned hydrogel presents synergistic topographical and biochemical cues for peripheral nerve regeneration. Nerve conduits filled with the aligned hydrogel can repair the long-distance sciatic nerve defects in 12 weeks. The function recovery facilitated by the aligned hydrogel is comparable with that of autografts. The aligned hydrogel upregulates regeneration-related genes and activates the PI3K/Akt and MAPK signaling pathways.
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