An injectable heparin-Laponite hydrogel bridge FGF4 for spinal cord injury by stabilizing microtubule and improving mitochondrial function

可注射肝素-Laponite 水凝胶桥接 FGF4,通过稳定微管和改善线粒体功能治疗脊髓损伤

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作者:Chenggui Wang, Zhe Gong, Xianpeng Huang, Jingkai Wang, Kaishun Xia, Liwei Ying, Jiawei Shu, Chao Yu, Xiaopeng Zhou, Fangcai Li, Chengzhen Liang, Qixin Chen

Conclusion

This promising sustained release system provides a synergistic effective approach to enhance recovery after SCI underlying a novel mechanism of axonal rehabilitation, and shows a translational prospect for the clinical treatment of SCI.

Methods

Characterization of Laponite, Laponite/Heparin (Lap/Hep) and Laponite/Heparin loaded with FGF4 (Lap/Hep@FGF4) hydrogels were measured by rheometer. Multiple comprehensive evaluations were used to detect motor functional recovery and the axonal rehabilitation after Lap/Hep@FGF4 treatment in vivo (SCI rat model). Moreover, microtubule dynamic and energy transportation, which regulated axonal regeneration was evaluated by Lap/Hep@FGF4 gel in vitro (primary neuron).

Results

FGF4 released from Lap/Hep gel locally achieves strong protection and regeneration after SCI. The Lap/Hep@FGF4 group revealed remarkable motor functional recovery and axonal regrowth after SCI through suppressing inflammatory reaction, increasing remyelination and reducing glial/fibrotic scars. Furthermore, the underlying mechanism of axonal rehabilitation were demonstrated via enhancing microtubule stability and regulating mitochondrial localization after Lap/Hep@FGF4 treatment.

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