Document Type

Article

Publication Date

11-2025

Publication Title

Advanced Healthcare Materials

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 (similar to 90% by electrical) are comparable with conventionally used chemical stimuli-based transdifferentiation protocols (similar to 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.

Comments

Metin Uz acknowledges support from the National Science Foundation, Division of Chemical, Bioengineering, Environmental, and Transport Systems (Award number 2227383). Surya Mallapragada acknowledges support from the Carol Vohs Johnson endowed chair. This work was supported in part by Chan Zuckerberg Initiative DAF and Silicon Valley Community Foundation dynamic imaging grant DAF2020-225394, in part by U.S. ARO grant W911NF2310042.

DOI

10.1002/adhm.202502204

Version

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