1. Department of Orthopedics Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, People's Republic of China 2. Department of orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
Rationale: Spinal cord injury (SCI) remains a critical clinical challenge. The controlled release of FGF4, a novel neuroprotective factor, from a versatile Laponite hydrogel to the injured site was a promising strategy to promote axon regeneration and motor functional recovery after 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.
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.
Wang C, Gong Z, Huang X, Wang J, Xia K, Ying L, Shu J, Yu C, Zhou X, Li F, Liang C, Chen Q. An injectable heparin-Laponite hydrogel bridge FGF4 for spinal cord injury by stabilizing microtubule and improving mitochondrial function. Theranostics 2019; 9(23):7016-7032. doi:10.7150/thno.37601. https://www.thno.org/v09p7016.htm
Wang C, Gong Z, Huang X, Wang J, Xia K, Ying L, Shu J, Yu C, Zhou X, Li F, Liang C, Chen Q. 2019. An injectable heparin-Laponite hydrogel bridge FGF4 for spinal cord injury by stabilizing microtubule and improving mitochondrial function. Theranostics. 9(23):7016-7032.
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