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Dual-Coupling Amplified Electrostimulaton Drives In Situ Bone Regeneration

ABSTRACT: Electrical stimulation is known to promote bone regeneration, but conventional systems often require wired connections or implanted power sources and provide limited stimulation to deep tissues. To address this, a dual-amplified body-coupled (DAB) electrostimulation approach was developed, enabling wireless deep-tissue stimulation by harvesting ambient low-frequency electrical fields. A conductive membrane electrode was chosen to focus electrical potentials at the bone-defect site, and both simulations and ex vivo measurements confirmed enhanced electric field intensity within bone tissue under DAB stimulation. To figure out the mechanistic insights, bulk RNA-seq analysis was conducted on DAB-stimulated human bone marrow mesenchymal stromal cells (hBMSCs) and their corresponding controls across multiple time points (Days 2, 4, 7, and 14). Differentially expressed gene (DEG) analysis revealed that by Day 14 of DAB treatment, osteogenic markers including BMP2, BMP6, and SPP1 were significantly upregulated, suggesting enhanced osteogenic differentiation, as these genes are integral to bone formation and mineralization processes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE324996 | GEO | 2026/03/21

REPOSITORIES: GEO

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Project description:Despite efforts to mature human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) for disease modeling and high throughput screening, cells remain immature and may not reflect adult biology. Recent advancements utilize electro-mechanical and paracrine stimulation to functionally mature cardiomyocytes, but the resulting engineered constructs continue to lack a microenvironment conducive to electrical signal propagation and maturity. Conductive polymers are attractive candidates to facilitate electrical communication between gaps in sparse hPSC-CM clusters or between hPSC-CMs to repair conduction defects. To create a conductive polymer platform for improved electrical signal propagation between hPSC-CMs and achieve electrical maturity, we electrospun poly(3,4-ethylendioxythiophene):polystyrene sulfonate (PEDOT:PSS) blended with 8% (w/v) poly(vinyl alcohol) (PVA). Matrix fiber structure remained stable over 4 weeks in buffer, stiffness remains near cardiac stiffness in vivo, and electrical conductivity scaled with PEDOT:PSS concentration. When fibroblasts were added to fibers, cells had higher initial attachment to PEDOT:PSS compared to PVA-only scaffolds, and after 5 days, over 90% of fibroblasts remained viable on PEDOT:PSS scaffolds compared to PVA-only scaffolds. Electrically excitable hPSC-CMs cultured on conductive substrates exhibited an upregulation of cardiac and muscle-related genes as opposed to non-conductive substrates. These cells further displayed increased desmoplakin (DP) localization on conductive scaffolds, indicating an improvement in the mechanical stability of our hPSC-CMs. Sarcomere organization also scaled with increasing PEDOT:PSS concentration, even in sub-monolayer cell densities, suggesting that improved organization of the contractile machinery in these cells was due to the electrical condition of the matrix. Calcium handling indicated higher calcium flux with a shorter time to peak, further suggesting improved electrical maturity, even when sub-confluent. Taken together, these data suggest that PEDOT:PSS/PVA scaffolds are stable, of a stiffness relevant to cardiomyocytes, and supportive of electrical coupling even in the absence of a monolayer, which may improve cardiac disease modeling and drug development.

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Dual-Coupling Amplified Electrostimulaton Drives In Situ Bone Regeneration

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