The promotion of neural regeneration in an extreme rat spinal cord injury model using a collagen scaffold containing a collagen binding neuroprotective protein and an EGFR neutralizing antibody.
In the treatment of spinal cord injury, implantation of scaffolding biomaterials and the addition of neuroprotective factors will promote neural regeneration. It has been demonstrated in our previous work that linear ordered collagen scaffold (LOCS) will bridge neural regeneration after the injury of spinal cord hemisection, and BDNF fused with a collagen binding domain (CBD-BDNF) can bind to collagen specifically to exert the neuroprotective effect. Besides neuroprotective factors, the lack of axon regeneration of the injured spinal cord has been attributed partially to regeneration inhibitors such as myelin associated proteins and chondroitin sulfate proteoglycans (CSPGs). Epidermal growth factor receptor (EGFR) activation is downstream of the signaling pathways of these inhibitors. Here, the monoclonal antibody, 151IgG that inhibits signaling of EGFR was used to neutralize EGFR. 151IgG was cross-linked to LOCS and CBD-BDNF bound to LOCS to make a triple-functional biomaterial for neural regeneration (bridging, prompting growth and neutralizing growth inhibitors). This triple-functional device was tested in a 6 mm transected SCI model. Results showed that this collagen scaffold with the addition of 151IgG and CBD-BDNF provided effective bridging and stimulation effects for neural regeneration, recovery of electrical transmission of synapses and preventing the formation of glial scars in the extreme transected rat SCI model.
Han
Qianqian
Q
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Jin
Wei
W
Xiao
Zhifeng
Z
Ni
Hongbin
H
Wang
Jinhuan
J
Kong
Jie
J
Wu
Jun
J
Liang
Weibang
W
Chen
Lei
L
Zhao
Yannan
Y
Chen
Bing
B
Dai
Jianwu
J
D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D004594:Electrophysiology; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000276:immunology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000628:therapy*; D054457:Tissue Scaffolds / Q000737:chemistry*
D057134:Antibodies, Neutralizing; D019208:Brain-Derived Neurotrophic Factor; D003094:Collagen; D066246:ErbB Receptors