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Peripheral nerve injuries (PNIs) have a significant impact on the quality of life for patients suffering from trauma or disease. In injuries with critical nerve gaps, PN regeneration requires tissue scaffolds with appropriate physiological properties that promote cell growth and functions. Hydrogel scaffolds represent a promising platform for engineering soft tissue constructs that meet key physiological requirements. Nonetheless, ongoing innovation remains essential, as current designs continue to fall short of replicating the functional performance of autografts in bridging critical-sized nerve defects. In this study, gelatin methacrylate (gelMA)-based hydrogels are evaluated to fully characterize their pore structure, compressive stiffness, viscoelasticity, and 3D bioprintability. Hyaluronic acid (HA) and single-walled carbon nanotubes (SWCNTs) are explored as gelMA additives to modify viscoelastic and electrically conductive properties, respectively. Finally, Schwann cell (SC) and human umbilical vein endothelial cell (HUVEC) growth and functions are quantified to assess the biocompatibility of the hydrogel composites as materials for nerve scaffold fabrication. It was found that the microstructure and mechanical properties of gelMA-based hydrogels can be precisely controlled by modifying the concentrations of each component. The addition of HA led to altered viscoelastic properties of the cured structures and SWCNTs increased electrical conductivity, with both additives maintaining cytocompatibility while influencing the protein expression of both SCs and HUVECs. These composite hydrogels have potential in PNI regeneration applications.
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Few‐Layered Conductive Graphene Foams for Electrical Transdifferentiation of Mesenchymal Stem Cells Into Schwann Cell‐Like Phenotypes
ABSTRACT This study investigates the potential of few‐layered conductive graphene foams as 3D platforms for the electrical transdifferentiation of mesenchymal stem cells (MSCs) into Schwann cell (SC)‐like phenotypes for peripheral nerve injury (PNI) treatment. The 3D graphene foams (3D‐GF) are cytocompatible with MSCs and created a favorable microenvironment for the cells to attach, grow, proliferate, and transdifferentiate. We demonstrated that MSCs cultured within 3D‐GF can be transdifferentiated into SC‐like phenotypes using the synergistic effects of electrical stimulation and 3D porous and conductive structure. Our immunocytochemistry and gene expression analyses showed the expression of Schwann cell markers and enhanced secretion of growth factors, suggesting successful transdifferentiation of MSCs into SC‐like phenotypes upon electrical stimulation. Our degree of transdifferentiation results (∼90% by electrical) are comparable with conventionally used chemical stimuli‐based transdifferentiation protocols (∼85% by chemical). The secreted growth factors are also biologically active, showing enhanced neurite outgrowth in PC12TrkB cells compared to the control. Our transcriptomics results also showed that the electrical stimulation‐directed transdifferentiation mainly occurs through MAPK signaling pathway activation. These findings suggest that conductive 3D‐GF could serve as a promising platform for peripheral nerve regeneration applications, offering a novel approach to enhance the transdifferentiation and functional properties of MSCs.
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- Award ID(s):
- 2227383
- PAR ID:
- 10662695
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/adhm.202502204
