Enhancement of sciatic nerve regeneration with dual delivery of vascular endothelial growth factor and nerve growth factor genes

Abstract

Background: Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomically the most challenging to regenerate given its length and large cross-sectional area. For the present, autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. However, this method sacrifices healthy nerves and requires highly intensive surgery, still calling for other advanced alternatives for nerve grafting. Results:In this study, we utilized previously well-established gene delivery system to dually deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), exploring therapeutics for sciatic nerve injury. Low-molecular-weight branched polyethylenimine (bPEI) was constructed as the backbone structure of gene vectors, and it was further crosslinked to synthesize degradable polycations via the conjugation of dialdehydes. Potential synergistic effect between VEGF and NGF proteins were observed on rat sciatic nerve crush injury model in this study. Conclusions:We concluded that dual delivery of plasmid VEGF and NGF as gene therapy could enhance sciatic nerve regeneration. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

hiPSC-derived 3D Bioprinted Skeletal Muscle Tissue Implants Regenerate Skeletal Muscle Following Volumetric Muscle Loss

“…We observed a 3-fold increase in VEGF secretion over the course of the second to third week after the induction of hiPSC-MPC differentiation, which contributed to axonal growth, angiogenesis and later muscle regeneration over the course of the in vivo study. [71][72][73][74][75] Overall, the vascularized hiPSC-MPC laden muscle constructs showed increased muscle regeneration, angiogenesis and maintenance of potent stem cells compared to control groups (V2 and V1). Together, these results provide a VML repair strategy based on pre-vascularized large-scale hiPSC-derived skeletal muscle implants.…”

Therapeutic Potential of Complementary and Alternative Medicines in Peripheral Nerve Regeneration: A Systematic Review

“…Additionally, a study on Ginkgo biloba extract showed that it promoted axonal angiogenesis through the modulation of related genes, including Vegf, Sox18, Prom1, and IL-6 [ 71 ]. Studies have also demonstrated the participation of Vegf [ 152 , 153 ], Prom1 [ 154 ], and another subfamily gene, Sox11 in sciatic nerve regeneration [ 155 ], and the restorative role of IL-6 has also been implied in DPN and central nervous system models [ 156 , 157 ]. Muscimol prevented hyperalgesia through the modulation of PMP22 [ 91 ], a key component of the basal lamina.…”

Anisotropic scaffolds for peripheral nerve and spinal cord regeneration

“…There is still a lack of clinically effective scaffolds. This may be due to inherent nerve complexities and a need for consideration of electrical stimulation, vascularization, and exogenous biochemical molecules [ [216] , [217] , [218] , [219] ].…”

“…The incorporation methods include physical embedding and surface immobilization. For example, a gene delivery system fabricated by polyethyleneimine was used to deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF), and regenerated microvessels in both peripheral nerves and gastrocnemius muscles can be seen after in vivo transfection [ 218 ]. Advanced 3D printing may also be able to print more precise scaffolds that can improve vascularization and further improve nerve graft survival and function.…”