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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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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