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 μm, and also had the ability to activate the PDGFRβ 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.

Calcium phosphate cement (CPC) has been widely studied, but its lack of osteoinductivity and inadequate mechanical properties limit its application, while strontium is able to promote bone formation and inhibit bone resorption. In this study, different proportions of tristrontium silicate were introduced to create a novel strontium-modified calcium phosphate cement (SMPC). The physicochemical properties of SMPC and CPC were compared, and the microstructures of the bone cements were characterized with scanning electron microscopy assays. Then, the effect of SMPC on cell proliferation and differentiation was examined. Furthermore, local inflammatory response and osteogenesis after SMPC implantation were also confirmed in the study. Finally, a rat model of isolated vertebral defects was used to test the biomechanical properties of the cements. The results showed that SMPC has better injectability and a shorter setting time than CPC. Meanwhile, the addition of tristrontium silicate promoted the mechanical strength of calcium phosphate cement, and the compressive strength of 5% SMPC increased to 6.00 ± 0.74 MPa. However, this promotion effect gradually diminished with an increase in tristrontium silicate, which was also found in the rat model of isolated vertebral defects. Furthermore, SMPC showed a more preferential role in promoting cell proliferation and differentiation compared to CPC. Neither SMPC nor CPC showed significant inflammatory responses in vivo. Histological staining suggested that SMPCs were significantly better than CPC in promoting new bone regeneration. Importantly, this osteogenesis effect of SMPC was positively correlated with the ratio of tristrontium silicate. In conclusion, 5% SMPC is a promising substitute material for bone repair with excellent physicochemical properties and biological activity.

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to partial or complete sensorimotor function loss of the limbs. Transplantation of exogenous neurons derived from stem cells to the lesion site becomes a new neurorestorative strategy for SCI treatment. Spermatogonial stem cells (SSCs) can attain pluripotency features by converting to embryonic stem-like cells in vitro. However, differentiating SSCs into lineage-specific neurons is quite difficult and low efficiency. Methods: Immunofluorescence, immunohistochemistry, Western blotting, whole-cell patch clamp, and behavioral tests were performed to verify that self-assembled hydrogels could improve the directional differentiation efficiency of SSCs and the feasibility of SSC-derived neurons in the treatment of spinal cord injury. Results:We developed a novel self-assembled peptide Nap-FFGEPLQLKMCDPGYIGSR (Nap-E7-YIGSR) coated with aligned electrospun PCL fibers to enhance neuronal differentiation of SSCs. The Nap-E7-YIGSR peptide could evenly self-assemble on the surface of PCL fibers, enhanced the materials's hydrophilicity, and improved the SSC affinity of PCL fibers through the stem cell adhesion peptide sequence EPLQLKM domain. In addition, Nap-E7-YIGSR could effectively induce SSC neuron differentiation by activating the integrin β1/GSK3β/β-catenin signaling pathway. Moreover, implanting the induced neurons derived from SSCs into SCI lesion sites in rats resulted in the formation of new relay circuits, myelination, and synapse formation. Furthermore, SSC-derived neurons could survive and function in the spinal cord injury microenvironment, boosting the recovery of locomotion. Conclusion:The combination of the multifunctional peptide and aligned fibers can potentially trigger SSC differentiation to neurons, facilitating neuronal replacement therapy and promoting functional recovery after SCI.