The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.

中文翻译：

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单独或与明胶-糠胺水凝胶结合的胶原蛋白结合肝细胞生长因子（HGF）增强了脊髓损伤后小鼠的功能恢复。

脊髓损伤（SCI）的治疗目前是一项重大挑战。肝细胞生长因子（HGF）是一种多能神经营养和神经再生因子，可有益于SCI的治疗。但是，针对细胞外基质的固定化HGF可能比可扩散的未修饰HGF更有效。在这项研究中，我们评估了具有胶原蛋白结合域（CBD-HGF）的工程化HGF的神经修复作用。单次给药后，CBD-HGF在脊髓中保留了7天，而在第1天几乎未见到未修饰的HGF。当明胶-糠胺（FA）水凝胶作为支架施加到受损的脊髓上时，CBD-HGF在明胶-FA水凝胶中保留了7天，而HGF褪色了1天。通过运动恢复以及电生理和免疫组织化学分析确定，与HGF相比，单次施用CBD-HGF可以增强脊髓压迫损伤的恢复能力。单独的CBD-HGF不能改善从完全横断损伤中的恢复，但是CBD-HGF与明胶-FA水凝胶的结合比HGF与水凝胶的结合更有效地促进了内源性修复和恢复。这些结果表明，工程化的CBD-HGF比单纯的HGF具有更好的治疗效果。CBD-HGF与水凝胶支架相结合可能有望用于治疗严重的SCI。然而，CBD-HGF结合明胶-FA水凝胶比HGF结合水凝胶更有效地促进了内源性修复和恢复。这些结果表明，工程化的CBD-HGF比单纯的HGF具有更好的治疗效果。CBD-HGF结合水凝胶支架可能有望用于治疗严重的SCI。然而，CBD-HGF结合明胶-FA水凝胶比HGF结合水凝胶更有效地促进了内源性修复和恢复。这些结果表明，工程化的CBD-HGF比单纯的HGF具有更好的治疗效果。CBD-HGF结合水凝胶支架可能有望用于治疗严重的SCI。