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Conductive and bioactive supramolecular scaffolds promote neuronal maturation [Stupp05_RNA-seq]

ABSTRACT: Traumatic injury in the central nervous system (CNS) results in neuronal damage and death, with chronic symptoms such as damaged cognition and paralysis. While chemically engineered scaffolds can be delivered to provide a substrate to stimulate axon regrowth, many grafts lack efficacy due to inefficient electrical coupling between the material and the conductive in vivo environment. We have incorporated a conductive component, functionalized poly[3,4-(ethelynedioxythiophene)] (PEDOT), into a supramolecular biomaterial scaffold which facilitates neuronal differentiation and maturation. Peptide amphiphiles (PAs) can self-assemble into high-aspect ratio nanostructures that mimic native extracellular matrix and may be functionalized with bioactive epitopes such as (previously described) laminin mimetic (IKVAV). Interestingly, this synthesized PEDOT:PA enhanced neurite length and branching in murine primary cortical neurons. Furthermore, protein analysis clearly showed PEDOT:PA upregulated maturation and pre-/post-synaptic markers (Map2, PSD 95, Syn). Moreover, human induced pluripotent stem cell (iPSCs) derived spinal cord neuron models showed enhanced differentiation of iPSCs into human spinal cord progenitors through increased expression of TUJ-1. These results strongly suggest that PEDOT:PA promotes CNS maturation in mouse and human systems and shows its potential as a therapeutic in spinal cord injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE303030 | GEO | 2026/06/01

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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Conductive and bioactive supramolecular scaffolds promote neuronal maturation [Stupp05_RNA-seq]

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