Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin-furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury

Kentaro Yamane, Tetsuro Mazaki, Yasuyuki Shiozaki, Aki Yoshida, Kensuke Shinohara, Mariko Nakamura, Yasuhiro Yoshida, Di Zhou, Takashi Kitajima, Masato Tanaka, Yoshihiro Ito, Toshifumi Ozaki, Akihiro Matsukawa

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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.

Original languageEnglish
Article number917
JournalScientific Reports
Issue number1
Publication statusPublished - Dec 1 2018


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