Linear ordered collagen scaffolds loaded with collagen-binding brain-derived neurotrophic factor improve the recovery of spinal cord injury in rats.
Growth factors such as brain-derived neurotrophic factor (BDNF) are widely used in the recovery of spinal cord injury (SCI) for promoting axonal regeneration or improving neuron survival. However, the lack of efficient delivery approaches limits their clinical applications. In this study, we constructed an efficient delivery system including collagen-binding BDNF and linear ordered collagen scaffolds (LOCS). A collagen-binding domain (CBD) was utilized to construct collagen-targeting BDNF (CBD-BDNF) to allow its specific binding to the collagen. In vitro activity assay showed that CBD-BDNF had similar bioactivity in neurite outgrowth of dorsal root ganglia and the survival of PC12 cells. CBD-BDNF was shown to have specific binding activity to collagen. Using the rat hemisection SCI model, we found that LOCS loaded with CBD-BDNF significantly improved the SCI recovery evaluated by the Basso, Beattie, and Bresnahan scale and immunohistochemical staining with anti-neurofilament antibody. Thus, this targeting drug delivery system consisting of CBD-BDNF and LOCS could be an effective strategy for the repair of SCI.
Han
Qianqian
Q
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Sun
Wenjie
W
Lin
Hang
H
Zhao
Wenxue
W
Gao
Yuan
Y
Zhao
Yannan
Y
Chen
Bing
B
Xiao
Zhifeng
Z
Hu
Wei
W
Li
Yuan
Y
Yang
Bo
B
Dai
Jianwu
J
D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D048091:Guided Tissue Regeneration / Q000379:methods*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000628:therapy*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D003094:Collagen