Supramolecular Hydrogel Microspheres of Platelet-Derived Growth Factor Mimetic Peptide Promote Recovery from Spinal Cord Injury

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 mu m, and also had the ability to activate the PDGFR beta of NSCs more effectively than PDGF-MPH. In vitro, PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo, PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.

Automated summary

A strategy of using PDGF-MP hydrogel microspheres instead of bulk hydrogels can enhance the efficiency of PDGF-MP in activating its receptor, thus improving the therapeutic ability of neural stem cells (NSCs) in treating spinal cord injuries (SCI). In vitro experiments showed that PDGF-MP hydrogel microspheres maintained the proliferation and inhibited the apoptosis of NSCs in the presence of myelin extracts. In vivo experiments demonstrated that PDGF-MP hydrogel microspheres inhibited inflammatory cell infiltration and cell apoptosis, and promoted axonal regeneration, synapse formation, and angiogenesis in SCI rats.