Functionalized collagen scaffold implantation and cAMP administration collectively facilitate spinal cord regeneration
| 作者： |
Han,Xianping Shang,Bin Wang,Bing Chen,Zhifeng Xiao,Jianwu Dai |
| 刊物名称： |
Acta Biomaterialia |
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| 发表年度： |
2015-11-26 |
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| 摘要： |
Previous studies have demonstrated that several mechanisms, including numerous inhibitory molecules, weak neurotrophic stimulation and deficient intrinsic regenerative responses, collectively contribute to the failure of mature spinal cord axon regeneration. Thus, combinatorial therapies targeting multiple mechanisms have attracted much attention. In the present study, a porous collagen scaffold was used to support neuronal attachment and bridge axonal regeneration. The scaffold was specifically functionalized using neutralizing proteins (CBD-EphA4LBD, CBD-PlexinB1LBD and NEP1-40) and collagen-binding neurotrophic factors (CBD-BDNF and CBD-NT3) to simultaneously antagonize myelin inhibitory molecules (ephrinB3, Sema4D and Nogo) and exert neurotrophic protection and stimulation. Cerebellar granular neurons cultured on the functionalized collagen scaffold promoted neurite outgrowth in the presence of myelin. Furthermore, a full combinatorial treatment comprising functionalized scaffold implantation and cAMP administration was developed to evaluate the synergistic repair ability in a rat T10 complete removal spinal cord injury model. The results showed that full combinatorial therapy exhibited the greatest advantage in reducing the volume of cavitation, facilitating axonal regeneration, and promoting neuronal generation. The newborn neurons generated in the lesion area could form the neuronal relay and enhance the locomotion recovery after severe spinal cord injury. |
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