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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(?-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 ?-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 microenvironment in vitro.

SUBMITTER: Rath R

PROVIDER: S-EPMC5193097 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Biomimetic microstructure morphology in electrospun fiber mats is critical for maintaining healthy cardiomyocyte phenotype.

Rath Rutwik R Lee Jung Bok JB Tran Truc-Linh TL Lenihan Sean F SF Galindo Cristi L CL Su Yan Ru YR Absi Tarek T Bellan Leon M LM Sawyer Douglas B DB Sung Hak-Joon HJ

Cellular and molecular bioengineering 20150908 1

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 de ...[more]

PMID: 28042345

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Project description:Electrospun fiber mats (EFMs) are highly versatile biomaterials used in a myriad of biomedical applications. Whereas some facets of EFMs are well studied and can be highly tuned (e.g., pore size, fiber diameter, etc.), other features are under characterized. For example, although substrate mechanics have been explored by several groups, most studies rely on Young's modulus alone as a characterization variable. The influence of fiber mat thickness and the effect of supports are variables that are often not considered when evaluating cell-mechanical response. To assay the role of these features in EFM scaffold design and to improve understanding of scaffold mechanical properties, we designed EFM scaffolds with varying thickness (50-200 µm) and supporting methodologies. EFM scaffolds were comprised of polycaprolactone and were either electrospun directly onto a support, suspended across an annulus (3 or 10 mm inner diameter), or "tension-released" and then suspended across an annulus. Then, single cell spreading (i.e., Feret diameter) was measured in the presence of these different features. Cells were sensitive to EFM thickness and suspended gap diameter. Overall, cell spreading was greatest for 50 µm thick EFMs suspended over a 3 mm gap, which was the smallest thickness and gap investigated. These results are counterintuitive to conventional understanding in mechanobiology, which suggests that stiffer materials, such as thicker, supported EFMs, should elicit greater cell polarization. Additional experiments with 50 µm thick EFMs on polystyrene and polydimethylsiloxane (PDMS) supports demonstrated that cells can "feel" the support underlying the EFM if it is rigid, similar to previous results in hydrogels. These results also suggest that EFM curvature may play a role in cell response, separate from Young's modulus, possibly because of internal tension generated. These parameters are not often considered in EFM design and could improve scaffold performance and ultimately patient outcomes.

Dataset Information

Biomimetic microstructure morphology in electrospun fiber mats is critical for maintaining healthy cardiomyocyte phenotype.

Publications

Biomimetic microstructure morphology in electrospun fiber mats is critical for maintaining healthy cardiomyocyte phenotype.

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