Nervous tract-bioinspired multi-nanoyarn model system regulating neural differentiation and its transcriptional architecture at single-cell resolution

Li, Zhiwei; Qi, Ye; Li, Zheng; Chen, Shaojuan; Geng, Huimin; Han, Jinming; Wang, Jiahao; Zhao-qing, Wang; Huang, Bin; Li, Gang; Li, Xingang; Wu, Shaohua; Ni, Shilei

doi:10.1016/j.biomaterials.2023.122146

Cited by 7 publications

(3 citation statements)

References 71 publications

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“…Therefore, we presume that growth cones and focal adhesion are the bridges between the ECM-mimicking cues of 3D NSs and neural cell behaviors by activating the CAM-based MAPK/phosphatidylinositol 3 kinase (PI3K)-protein kinase B (AKT) signaling cascade. The potential mechanism was also verified with our previous report about 3D electrospinning scaffolds in vitro , and the in vivo performance of biomimetic scaffolds was explored in this study 53 .…”

Section: Discussionsupporting

confidence: 87%

Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration

Li,

Qi,

Sun

et al. 2023

Theranostics

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Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to severe neurological dysfunction and even permanent paralysis. A strategy combining biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for SCI treatment. Methods: Innovative three-dimensional (3D) nanofibrous sponges (NSs) were designed and developed by a combination of directional electrospinning and subsequent gas-foaming treatment. Immunofluorescence, mRNA sequencing, magnetic resonance imaging, electrophysiological analysis, and behavioral tests were used to investigate the in vitro and in vivo regenerative effects of the 3D NSs. Results: The generated 3D NSs exhibited uniaxially aligned nano-architecture and highly controllable hierarchical structure with super-high porosity (99%), outstanding hydrophilicity, and reasonable mechanical performance. They facilitated cell infiltration, induced cell alignment, promoted neuronal differentiation of NSCs, and enhanced their maturation mediated through cellular adhesion molecule pathways. In vivo , the NSC-seeded 3D NSs efficiently promoted axon reinnervation and remyelination in a rat SCI model, with new “neural relays” developing across the lesion gap. These histological changes were associated with regain of function, including increasing the neurological motor scores of SCI rats, from approximately 2 to 16 (out of 21), and decreasing the sensing time in the tape test from 140 s to 36 s. Additionally, the scaffolds led to restoration of ascending and descending electrophysiological signalling. Conclusion: The as-fabricated 3D NSs effectively regulate NSC fates, and an advanced combination of 3D NS design and transplanted NSCs enables their use as an ideal tissue-engineered scaffold for SCI repair.

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Section: Discussionsupporting

confidence: 87%

Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration

Li,

Qi,

Sun

et al. 2023

Theranostics

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“…6 I and J and SI Appendix , Fig. S34 ), which is associated with neurite growth ( 36 ). It is worth noting that the regenerated axons in the TPC group also exhibited the most robust remyelination capacity, which aided axon metabolism and signal conduction according to luxol fast blue (LFB) staining ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Restoring neuronal iron homeostasis revitalizes neurogenesis after spinal cord injury

Geng,

Li,

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Spinal cord injury (SCI) can lead to iron overloading and subsequent neuronal ferroptosis, which hinders the recovery of locomotor function. However, it is still unclear whether the maintenance of neuronal iron homeostasis enables to revitalize intrinsic neurogenesis. Herein, we report the regulation of cellular iron homeostasis after SCI via the chelation of excess iron ions and modulation of the iron transportation pathway using polyphenol-based hydrogels for the revitalization of intrinsic neurogenesis. The reversed iron overloading can promote neural stem/progenitor cell differentiation into neurons and elicit the regenerative potential of newborn neurons, which is accompanied by improved axon reinnervation and remyelination. Notably, polyphenol-based hydrogels significantly increase the neurological motor scores from ~8 to 18 (out of 21) and restore the transmission of sensory and motor electrophysiological signals after SCI. Maintenance of iron homeostasis at the site of SCI using polyphenol-based hydrogels provides a promising paradigm to revitalize neurogenesis for the treatment of iron accumulation-related nervous system diseases.

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“…All these progresses have been inevitably based on the innovations of electrospinning spinneret [ 27 , 28 ]. However, most of electrospun nanofibers are collected as the randomly oriented structure, which lack of a capacity to regulate the cell migration and control the cell orientation [ 29 , 30 ]. The existing study has fabricated uniaxially aligned nanofiber mats and demonstrated their superiority compared with randomly oriented nanofiber mats [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Electrospun radially oriented berberine-PHBV nanofiber dressing patches for accelerating diabetic wound healing

Wang,

Zhang,

Jiang

et al. 2024

Regenerative Biomaterials

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A dressing patch made of radially oriented poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers was successfully manufactured with a modified electrospinning strategy. The as-electrospun PHBV radially oriented nanofiber dressing patch exhibited uniform and bead-free nanofibrous morphology and innovative radially oriented arrangement, which was demonstrated to possess obviously improved mechanical property, increased surface hydrophilicity, and enhanced biological properties compared to the PHBV nanofiber dressing patch control with traditionally randomly oriented pattern. Interestingly, it was found that the radially oriented pattern could induce the cell migration from the periphery to the center along the radially oriented nanofibers in a rapid manner. In order to further improve the bio-function of PHBV radially oriented nanofiber dressing patch, berberine (Beri, an isoquinoline alkaloid) with two different concentrations were encapsulated into PHBV nanofibers during electrospinning, which were found to present a sustained drug release behavior for nearly one month. Importantly, the addition of Beri could impart the dressing patch with excellent anti-inflammatory property by significantly inhibiting the secretion of pro-inflammatory factors of M1 macrophages, and also showed an additive influence on promoting the proliferation of human dermal fibroblasts (HDFs), as well as inhibiting the growth of E. coli, S. aureus, and C. albicans, compared with the Beri-free dressing patch. In the animal studies, the electrospun PHBV radially oriented nanofiber dressing patch loading with high Beri content was found to obviously accelerate the healing process of diabetic mouse full-thickness skin wound with shortened healing time (100% wound closure rate after 18 days’ treatment) and improved healing quality (improved collagen deposition, enhanced re-epithelialization and neovascularization, and increased hair follicles). In all, this study reported an innovative therapeutic strategy integrating the excellent physical cues of electrospun PHBV radially oriented nanofiber dressing patch with the multiple biological cues of Beri for the effective treatment of hard-to-heal diabetic wounds.

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Nervous tract-bioinspired multi-nanoyarn model system regulating neural differentiation and its transcriptional architecture at single-cell resolution

Cited by 7 publications

References 71 publications

Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration

Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration

Restoring neuronal iron homeostasis revitalizes neurogenesis after spinal cord injury

Electrospun radially oriented berberine-PHBV nanofiber dressing patches for accelerating diabetic wound healing

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