Peripheral Nerve Regeneration with 3D Printed Bionic Scaffolds Loading Neural Crest Stem Cell Derived Schwann Cell Progenitors

Abstract

Peripheral nerve injuries are one of the most common types of traumatic damage to the nervous system. Treatment of peripheral nerve injuries aims to promote axon regrowth by imitating and improving the microenvironment for sciatic nerve regeneration. In this study, regeneration efficiency and behavior of peripheral nerves are compared under three treatment strategies: 1) transplantation of Schwann cell progenitors induced from purified neural crest stem cells; 2) implantation of a multiscale scaffold based on high‐resolution 3D printing; and 3) implantation of this bionic scaffold loading Schwann cell progenitors. The results of structural, electrophysiological, and behavioral tests demonstrate that the three treatment strategies result in different degrees of regeneration. The purified neural crest stem cells differentiate into functional Schwann cells and promote axon regeneration. The multifunctional 3D printed scaffold promotes oriented growth and myelination, and the myelinated nerve regrows with increased density and without visible scaffolds after six months. For the regeneration, scaffold treatment produces better performance than cell graft alone. Finally, it is shown that implantation of multiscale scaffolds preloaded with neural crest stem cell derived Schwann cell progenitors is the best strategy to promote peripheral nerve regeneration with improved anatomy and function among the three different strategies.

Neural tissue engineering: From bioactive scaffolds and in situ monitoring to regeneration

“…Reproduced with permission. [51] Copyright 2017, American Chemical Society. (D) SEM and fluorescence micrographs (left) showing the structure of the 3D printed scaffold and the growth of NCSCs (green) on the scaffold, respectively.…”

“…[50] Electrospun aligned fibers with appropriate properties could effectively induce the differentiation of BMSCs to SCs after culturing in a differentiation medium, promoting the neurites extension of DRG (Figure 4C). [51] Neural crest stem cells (NCSCs) were differentiated into SCs on a 3D printed scaffold, leading to the formation of thicker myelin sheath with a higher density in a 6-mm rat sciatic nerve injury model (Figure 4D). [52] It is important to manipulate the differentiation route of the incorporated cells, clarify the differentiation mechanism, and guide the cells to desired phenotype to improve cell survival, safety, and efficacy.…”

Tacrolimus-Induced Neurotrophic Differentiation of Adipose-Derived Stem Cells as Novel Therapeutic Method for Peripheral Nerve Injury

“…In another study, GFP-labeled neural crest stem cells (NCSCs) were pre-induced into Schwann cell precursors before loading onto the nerve scaffolds. At 5 weeks after in vivo transplantation, most GFP-expressing cells in the nerve defect expressed SC markers S100β and P0, which demonstrated that NCSCs differentiated into SCs in vivo ( Li et al, 2021a ). Similarly, Li et al transplanted GFP-labeled NCSCs to transected spinal cord via seeding NSCs onto collagen scaffolds ( Li X. et al, 2016 ).…”

Small Structure, Large Effect: Functional Surfaces Inspired by Salvinia Leaves

“…It is an advanced manufacturing technology that can rapidly print 3D objects with the help of computers and has been widely used to prepare bionic structures. [ 64–66 ] In addition, 3D printing can effectively simulate the microstructure of the Salvinia blade and accurately replicate the original natural structure.…”