Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 24, Issue 14, Pages 8166-8178Publisher
WILEY
DOI: 10.1111/jcmm.15478
Keywords
basic fibroblast growth factor (bFGF); heparin-poloxamer (HP) hydrogel; nerve growth factor (NGF); neuroprotection; spinal cord injury
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Funding
- National Natural Science Funding of China [81801233, 81802238, 81760230, 81722028, 81972150]
- Zhejiang Provincial Natural Science Foundation of China [LQ18H090008, LR18H50001]
- Jiangxi Provincial Natural Science Foundation [20171BAB20503]
- Gannan Medical College Graduate Innovation Project [YC2018-X0014]
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The application of growth factors (GFs) for treating chronic spinal cord injury (SCI) has been shown to promote axonal regeneration and functional recovery. However, direct administration of GFs is limited by their rapid degradation and dilution at the injured sites. Moreover, SCI recovery is a multifactorial process that requires multiple GFs to participate in tissue regeneration. Based on these facts, controlled delivery of multiple growth factors (GFs) to lesion areas is becoming an attractive strategy for repairing SCI. Presently, we developed a GFs-based delivery system (called GFs-HP) that consisted of basic fibroblast growth factor (bFGF), nerve growth factor (NGF) and heparin-poloxamer (HP) hydrogel through self-assembly mode. This GFs-HP was a kind of thermosensitive hydrogel that was suitable for orthotopic administration in vivo. Meanwhile, a 3D porous structure of this hydrogel is commonly used to load large amounts of GFs. After single injection of GFs-HP into the lesioned spinal cord, the sustained release of NGF and bFGF from HP could significantly improve neuronal survival, axon regeneration, reactive astrogliosis suppression and locomotor recovery, when compared with the treatment of free GFs or HP. Moreover, we also revealed that these neuroprotective and neuroregenerative effects of GFs-HP were likely through activating the phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signalling pathways. Overall, our work will provide an effective therapeutic strategy for SCI repair.
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