Abstract
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.
Highlights
Hepatocyte growth factor (HGF), initially identified as a mitogenic factor for primary hepatocytes, is a multipotent neurotrophic and neuroregenerative factor with a wide variety of biological functions in the nervous system
HGF was barely seen on day 1, collagen-binding domain (CBD)-HGF showed a strong signal that remained until day 7 (Fig. 1a)
HGF had diffused and faded by day 1, while a much stronger CBD-HGF signal was seen on day 1 relative to HGF and the signal was present at day 7 (Fig. 1c)
Summary
Hepatocyte growth factor (HGF), initially identified as a mitogenic factor for primary hepatocytes, is a multipotent neurotrophic and neuroregenerative factor with a wide variety of biological functions in the nervous system. HGF promotes endogenous repair and functional recovery after SCI in rats[10] and marmosets[12]. As a tissue-engineering approach, scaffolds have been attracting increasing attention[14,15] as they provide an environment for cell attachment, proliferation and differentiation. Hydrogels are leading candidates for engineered tissue scaffolds due to their unique compositional and structural similarities to the natural extracellular matrix[16]. Gelatin-FA effectively delivered collagen-binding bone morphogenetic protein-4 (CBD-BMP4) cells and to affected sites, enhancing osteogenesis[18]. CBD-HGF combined with gelatin-FA hydrogel successfully promoted neural regeneration from a severe complete injury. A tissue engineering strategy composed of collagen-binding HGF and a gelatin scaffold is promising for the treatment of SCI
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
