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Peripheral nerve defects caused by trauma, tumors and other factors are common and difficult problems in clinical practice. Schwann cells are the most critical functional cells in the process of peripheral nerve regeneration. Their reduced proliferation ability and functional impairment in nerve scaffolds are the main obstacles to poor nerve defect effects.
Recently, the research results entitled "Bioactive MgO/MgCO3/Polycaprolactone Multi-gradient Fibers Facilitate Peripheral Nerve Regeneration by Regulating Schwann Cell Function and Activating Wingless/integrase-1 Signaling" were published in Advanced Fiber Materials by the collaboration of Professor Wang Deli of Peking University Shenzhen Hospital, Professor Li Ye of Hong Kong Polytechnic University, and Professor Zhang Jin of Fuzhou University. This work uses electrospinning technology to mix polycaprolactone (PCL) with magnesium-containing monomers (MgO, MgCO3) of different concentrations and different degradation efficiencies to prepare gradient nanofiber membranes with long-term sustained release of Mg2+. The regulation of the local nerve regeneration microenvironment is achieved by constructing a reasonable and effective Mg2+ sustained release system. The results of the study on the 10 mm sciatic nerve defect model of SD rats showed that the material can promote the myelination of regenerated axons, reinnervation of muscle tissue, and promote the regeneration of peripheral nerve function.
The main point of this paper
Preparation of multilayer nanofiber membrane:
A three-layer nanofiber membrane was synthesized by electrospinning PCL and different concentrations of magnesium monomers (MgO and MgCO3), in which the ratio of MgO/MgCO3 decreased layer by layer, forming a multi-gradient structure with a gradually decreasing Mg monomer concentration from the inside to the outside
Regulation of Mg2+ release:
The release of Mg2+ can be effectively controlled by adjusting the ratio of MgO (fast degradation) and MgCO3 (slow degradation). The sustained release performance of the material is mainly affected by the total concentration of Mg monomers and the ratio of MgO to MgCO3
In vitro degradation characteristics:
In vitro experiments evaluated the degradation characteristics of MgO/MgCO3/PCL, and the results showed that 10% MgO/MgCO3/PCL could efficiently and stably release Mg2+ within 6 weeks and reached a plateau after 7 weeks
Effect of Mg2+ on nerve regeneration:
Mg2+ promoted the growth of DRG neuron axons in a concentration-dependent manner. Higher axon growth density and length were observed in the 10 mmol/L and 20 mmol/L Mg2+ groups. Mg2+ can also enhance the interaction between Schwann cells (SCs) and neuronal axons, and promote the migration of SCs along the direction of axon growth
The effect of Mg2+ on SCs:
Mg2+ can induce the proliferation of primary SCs and show concentration-dependent characteristics. The SCs in the experimental group with Mg2+ are more extended in morphology, and the cell adhesion area is significantly increased, which is consistent with the morphological characteristics of the repair phenotype rSCs
The role of Mg2+ in nerve regeneration:
Mg2+ upregulates the expression of multiple axon induction factors, and provides necessary support and guidance for nerve regeneration by secreting neurotrophic factors and interacting with neuronal cells.
In vivo performance evaluation:
The in vivo performance of MgO/MgCO3/PCL multi-gradient nanofiber membrane was evaluated by using a 10 mm sciatic nerve defect model in SD rats.
Nerve continuity recovery:
Nerve continuity was observed to be restored in the experimental group 6 weeks after surgery, and regenerated nerve tissue was visible in the nerve conduit.
Nerve repair effect:
Histological evaluation 12 weeks after surgery showed that the nerve repair effect of the implanted MgO/MgCO3/PCL multi-gradient nanofiber membrane was significant compared with the negative control group (PCL nerve conduit).
Best repair effect:
The 10% MgO/MgCO3/PCL group showed the best repair effect, which may be related to its higher Mg2+ release rate in the initial 6 weeks of nerve regeneration.
Myelin regeneration evaluation:
Through toluidine blue staining and transmission electron microscopy (TEM) analysis, it was found that the autologous nerve transplantation group had obvious myelin regeneration, while the number, size and myelin thickness of myelinated axons in the 10% MgO/MgCO3/PCL nerve conduit group were significantly increased.
Effect of Mg2+:
The results showed that Mg2+ plays an important role in promoting axonal myelination.
Function of Schwann cells:
Schwann cells are mainly involved in the process of nerve regeneration. The continuous release of Mg2+ by MgO/MgCO3/PCL multi-gradient fibers may affect the function of Schwann cells in the middle and late stages of nerve regeneration.
In summary, this study used electrospinning technology to develop a gradient nanofiber membrane composed of MgO/MgCO3/PCL, and achieved long-term controllable release of Mg2+ by adjusting the concentration of Mg monomer. The in vivo performance of the material was evaluated using a 10 mm sciatic nerve defect model in SD rats, indicating that it helps promote peripheral nerve regeneration and restore motor function. In the middle and late stages of nerve regeneration, the controlled release of Mg2+ contributes to the myelination process of regenerated axons. The above research results not only reveal the great application prospects of magnesium-containing biomaterials in the treatment of neurological diseases, but also provide a solid theoretical basis for future technological applications and clinical transformation.
