摘要
Injectable biomaterial-based treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury(SCI)by bridging cavity spaces.However,there are limited reports of injectable,electroconductive hydrogels with self-healing properties being employed for the treatment of traumatic SCI.Hence,a natural extracellular matrix(ECM)biopolymer(chondroitin sulphate and gelatin)-based hydrogel containing polypyrrole,which imparted electroconductive properties,is developed for traumatic SCI repair.The resulting hydrogels showed mechanical(~928 Pa)and conductive properties(4.49 mS/cm)similar to natural spinal cord tissues.Moreover,the hydrogels exhibited shear-thinning and self-healing abilities,which allows it to be effectively injected into the injury site and to fill the lesion cavity to accelerate the tissue repair of traumatic SCI.In vitro,electroconductive ECM hydrogels promoted neuronal differentiation,enhanced axon outgrowth,and inhibited astrocyte differentiation.The electroconductive ECM hydrogel activated endogenous neural stem cell neurogenesis in vivo(n=6),and induced myelinated axon regeneration into the lesion site via activation of the PI3K/AKT and MEK/ERK pathways,thereby achieving significant locomotor function restoration in rats with spinal cord injury(p<0.001,compared to SCI group).Overall,the injectable self-healing electroconductive ECM-based hydrogels developed in this study are ideal biomaterials for treatment of traumatic SCI.
基金
We thank L.Fan for his help in drawing the schematic diagram and typesetting figures.This work was supported by the National Natural Science Foundation of China(Nos.51932002,51903087,and 31771080)
the Science and Technology Innovation Team Project of Foshan(No.2018IT100101)
Sino-Singapore International Joint Research Institute(No.203-A018004)
and the Joint Fund of Ministry of Education for Equipment Preresearch(No.6141A02022632).
