title: Biomimetic microstructure morphology in electrospun fiber mats is critical for maintaining healthy cardiomyocyte phenotype.
abstract: Despite recent advances in biomimetic substrates, there is still only limited understanding of how the extracellular matrix (ECM) functions in the maintenance of cardiomyocyte (CM) phenotype. In this study, we designed electrospun substrates inspired by morphologic features of non-failing and failing human heart ECM, and examined how these substrates regulate phenotypes of adult and neonatal rat ventricular CMs (ARVM and NRVM, respectively). We found that poly(ε-caprolactone) fiber substrates designed to mimic the organized ECM of a non-failing human heart maintained healthy CM phenotype (evidenced by cell morphology, organized actin/myomesin bands and expression of β-MYH7 and SCN5A.1 and SCN5A.2) compared to both failing heart ECM-mimetic substrates and tissue culture plates. Moreover, culture of ARVMs and NRVMs on aligned substrates showed differences in m- and z-line alignment; with ARVMs aligning parallel to the ECM fibers and the NRVMs aligning perpendicular to the fibers. The results provide new insight into cardiac tissue engineering by illustrating the importance models that mimic the cardiac ECM microenvironmentin vitro.
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN.
authors.forename: Rutwik
authors.initials: R
authors.lastname: Rath
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN.
authors.forename: Jung Bok
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Department of Medicine, Cardiovascular Division, Vanderbilt University, Nashville, TN.
authors.forename: Truc-Linh
authors.initials: TL
authors.lastname: Tran
authors.affiliation: Department of Medicine, Cardiovascular Division, Vanderbilt University, Nashville, TN.
authors.forename: Sean F
authors.initials: SF
authors.lastname: Lenihan
authors.affiliation: Department of Medicine, Cardiovascular Division, Vanderbilt University, Nashville, TN.
authors.forename: Cristi L
authors.initials: CL
authors.lastname: Galindo
authors.affiliation: Department of Medicine, Cardiovascular Division, Vanderbilt University, Nashville, TN.
authors.forename: Yan Ru
authors.initials: YR
authors.lastname: Su
authors.affiliation: Department of Cardiothoracic Surgery, Vanderbilt University, Nashville, TN.
authors.forename: Tarek
authors.initials: T
authors.lastname: Absi
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN; Department of Mechanical Engineering, Vanderbilt University, Nashville, TN.
authors.forename: Leon M
authors.initials: LM
authors.lastname: Bellan
authors.affiliation: Department of Medicine, Cardiovascular Division, Vanderbilt University, Nashville, TN.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Sawyer
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN; Department of Medicine, Cardiovascular Division, Vanderbilt University, Nashville, TN.
authors.forename: Hak-Joon
authors.initials: HJ
authors.lastname: Sung