Bionic microenvironment-inspired synergistic effect of anisotropic micro-nanocomposite topology and biology cues on peripheral nerve regeneration

Abstract

Anisotropic topographies and biological cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, their synergetic influence on injured peripheral nerve is rarely reported. In the present study, we constructed a bionic microenvironment-inspired scaffold integrated with both anisotropic micro-nanocomposite topographies and IKVAV peptide. The results showed that both the topographies and peptide displayed good stability. The scaffolds could effectively induce the orientation growth of Schwann cells and up-regulate the genes and proteins relevant to myelination. Last, three signal pathways including the Wnt/β-catenin pathway, the extracellular signal–regulated kinase/mitogen-activated protein pathway, and the transforming growth factor–β pathway were put forward, revealing the main path of synergistic effects of anisotropic micro-nanocomposite topographies and biological cues on neuroregeneration. The present study may supply an important strategy for developing functional of artificial nerve implants.

Application of Hybrid Electrically Conductive Hydrogels Promotes Peripheral Nerve Regeneration

“…As the gold standard, the application of nerve transplantation therapy is limited because of the shortage of donor nerves and the functional damage of donor nerve target organs. In this context, the strategy of using tissue engineering to repair PNI has gradually attracted the attention of researchers [ 77 , 78 , 79 ]. Several studies have proven that CHs have great advantages in repairing PNI.…”

Non-destructive monitoring of 3D cell cultures: new technologies and applications

“…This is a key feature of in vivo biology, connected with changes in gene expression ( Tajik et al, 2016 ) and behaviour ( Liverani et al, 2019 ), whose study in the lab has been enabled by 3D cell cultures. As an example, in vivo -like cell alignment, induced by the surrogate ECM features, was shown to result in improved tissue regeneration and repair ( Lu et al, 2021 ; Li et al, 2021a ). While a comprehensive analysis of cell–cell and cell-environment interactions is beyond the scope of this review, the interested reader is referred to Delle Cave et al (2021) and Bechtel et al (2021) for more information.…”

Anisotropic Silk-Inspired Nerve Conduit with Peptides Improved the Microenvironment for Long-Distance Peripheral Nerve Regeneration

“…28,29 Specifically, the microgrooved surface structure has been reported to facilitate the cell growth and development of SCs and achieve aligned axon growth, which reduces the wrong target reinnervation. 30,31 Athough RGD peprtides as biological signals or anisotropic topography as a key physical factor to provide guidence cues has been explored for directing axon regeneration and nerve repair indepently, the desirable repair of large-gap peripheral nerve injuries with functional recovery still remains a great challenge. Therefore, it is necessary to develop bioengineered NGCs with therapeutic multicues to achieve improved peripheral nerve regeneration.…”

“…Accordingly, the expression of Ncam was significantly lower in SCs on SFRGD hydrogels, indicating that the SFRGD hydrogel holds stronger capacity on promoting myelination of SCs because the RGD can enhance the adhesion and myelinogenic capability of SCs via interactions with α5β1 integrins to create appropriate cell adhesion sites on the surface of the scaffolds, which can further initiate myelination-associated intracellular signaling cascades such as the TGF-β pathway. 19,30 Meanwhile, for T30 hydrogels, the expressions of both Pmp22 and Krox20 were also significantly higher, indicating that hydrogels with grooved micropatterns can not only direct cell growth of SCs but also promisingly promote the myelination process of SCs for axon regeneration (Figure 4f). Dorsal root ganglion (DRG) as a sensory neuron plays a key role in the recovery of neurosensory function, which exists in both the peripheral nervous system and the central nervous system.…”

“…Based on superior spatial and temporal precision of light, the phototriggered gelation system has been regarded as a powerful tool for introducing biochemical signals to scaffolds in a noninvasive and highly controllable manner for directing cell fate. − Significantly, due to the high efficiency of rapid photochemistry upon simple irradiation, photo-cross-linking reactions provide a multifunctional strategy not only to incorporate biomolecules but also to spatially create robust physical microenvironments within biomaterials, such as surface topographic structure and stiffening and softening regions. , Currently, introducing anisotropic topography, a key physical factor of biomedical materials has shown success in promoting axon regeneration. , Specifically, the microgrooved surface structure has been reported to facilitate the cell growth and development of SCs and achieve aligned axon growth, which reduces the wrong target reinnervation. , …”