Conductive electrospun polymer improves stem cell-derived cardiomyocyte function and maturation.
Calcium handling
Desmoplakin
FluoVolt
Sarcomere organization
poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)
poly(vinyl) alcohol (PVA)
Journal
Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
02
06
2023
revised:
16
10
2023
accepted:
20
10
2023
medline:
6
11
2023
pubmed:
29
10
2023
entrez:
28
10
2023
Statut:
ppublish
Résumé
Despite numerous efforts to generate mature human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), cells often remain immature, electrically isolated, and may not reflect adult biology. Conductive polymers are attractive candidates to facilitate electrical communication between hPSC-CMs, especially at sub-confluent cell densities or diseased cells lacking cell-cell junctions. Here we electrospun conductive polymers to create a conductive fiber mesh and assess if electrical signal propagation is improved in hPSC-CMs seeded on the mesh network. Matrix characterization indicated fiber structure remained stable over weeks in buffer, scaffold stiffness remained near in vivo cardiac stiffness, and electrical conductivity scaled with conductive polymer concentration. Cells remained adherent and viable on the scaffolds for at least 5 days. Transcriptomic profiling of hPSC-CMs cultured on conductive substrates for 3 days showed upregulation of cardiac and muscle-related genes versus non-conductive fibers. Structural proteins were more organized and calcium handling was improved on conductive substrates, even at sub-confluent cell densities; prolonged culture on conductive scaffolds improved membrane depolarization compared to non-conductive substrates. Taken together, these data suggest that blended, conductive scaffolds are stable, supportive of electrical coupling in hPSC-CMs, and promote maturation, which may improve our ability to model cardiac diseases and develop targeted therapies.
Identifiants
pubmed: 37898021
pii: S0142-9612(23)00371-X
doi: 10.1016/j.biomaterials.2023.122363
pii:
doi:
Substances chimiques
Polymers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
122363Subventions
Organisme : NIBIB NIH HHS
ID : DP2 EB029757
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG045428
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL163996
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Adam J. Engler, Shadi A. Dayeh, Alyssa R. Holman reports financial support was provided by National Institutes of Health. Aileena C. Nelson reports financial support was provided by American Heart Association Inc. Gisselle Gonzalez, Erin LaMontagne, Alexander J. Whitehead reports financial support was provided by National Science Foundation.