Increased cardiomyocyte alignment and intracellular calcium transients using micropatterned and drug-releasing poly(glycerol sebacate) elastomers

Chenghao Zhu, Andrew E. Rodda, Vinh X. Truong, Yue Shi, Kun Zhou, John M. Haynes, Bing Wang, Wayne D. Cook, John S. Forsythe

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Myocardial tissue engineering is a promising therapy for myocardial infarction recovery. The success of myocardial tissue engineering is likely to rely on the combination of cardiomyocytes, pro-survival regulatory signals, and a flexible biomaterial structure that can deliver them. In this study, poly (glycerol sebacate) (PGS), which exhibits stable elasticity under repeated tensile loading, was engineered to provide physical features that aligned cardiomyocytes in a similar manner to that seen in native cardiac tissue. In addition, a small molecule mimetic of brain derived neurotrophic factor (BDNF) was polymerised into the PGS to achieve a continuous and steady release. Micropatterning of PGS elastomers increased cell alignment, calcium transient homogeneity and cell connectivity. The intensity of the calcium transients in cardiomyocytes was enhanced when cultured on PGS which released a small molecule BDNF mimetic. This study demonstrates that robust micropatterned elastomer films are a potential candidate for the delivery of functional cardiomyocytes and factors to the injured or dysfunctional myocardium, as well as providing novel in vitro platforms to study cardiomyocyte physiology.

Original languageEnglish
Pages (from-to)2494-2504
Number of pages11
JournalACS Biomaterials Science and Engineering
Volume4
Issue number7
DOIs
Publication statusPublished - 2018

Cite this

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title = "Increased cardiomyocyte alignment and intracellular calcium transients using micropatterned and drug-releasing poly(glycerol sebacate) elastomers",
abstract = "Myocardial tissue engineering is a promising therapy for myocardial infarction recovery. The success of myocardial tissue engineering is likely to rely on the combination of cardiomyocytes, pro-survival regulatory signals, and a flexible biomaterial structure that can deliver them. In this study, poly (glycerol sebacate) (PGS), which exhibits stable elasticity under repeated tensile loading, was engineered to provide physical features that aligned cardiomyocytes in a similar manner to that seen in native cardiac tissue. In addition, a small molecule mimetic of brain derived neurotrophic factor (BDNF) was polymerised into the PGS to achieve a continuous and steady release. Micropatterning of PGS elastomers increased cell alignment, calcium transient homogeneity and cell connectivity. The intensity of the calcium transients in cardiomyocytes was enhanced when cultured on PGS which released a small molecule BDNF mimetic. This study demonstrates that robust micropatterned elastomer films are a potential candidate for the delivery of functional cardiomyocytes and factors to the injured or dysfunctional myocardium, as well as providing novel in vitro platforms to study cardiomyocyte physiology.",
author = "Chenghao Zhu and Rodda, {Andrew E.} and Truong, {Vinh X.} and Yue Shi and Kun Zhou and Haynes, {John M.} and Bing Wang and Cook, {Wayne D.} and Forsythe, {John S.}",
year = "2018",
doi = "10.1021/acsbiomaterials.8b00084",
language = "English",
volume = "4",
pages = "2494--2504",
journal = "ACS Biomaterials Science and Engineering",
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TY - JOUR

T1 - Increased cardiomyocyte alignment and intracellular calcium transients using micropatterned and drug-releasing poly(glycerol sebacate) elastomers

AU - Zhu, Chenghao

AU - Rodda, Andrew E.

AU - Truong, Vinh X.

AU - Shi, Yue

AU - Zhou, Kun

AU - Haynes, John M.

AU - Wang, Bing

AU - Cook, Wayne D.

AU - Forsythe, John S.

PY - 2018

Y1 - 2018

N2 - Myocardial tissue engineering is a promising therapy for myocardial infarction recovery. The success of myocardial tissue engineering is likely to rely on the combination of cardiomyocytes, pro-survival regulatory signals, and a flexible biomaterial structure that can deliver them. In this study, poly (glycerol sebacate) (PGS), which exhibits stable elasticity under repeated tensile loading, was engineered to provide physical features that aligned cardiomyocytes in a similar manner to that seen in native cardiac tissue. In addition, a small molecule mimetic of brain derived neurotrophic factor (BDNF) was polymerised into the PGS to achieve a continuous and steady release. Micropatterning of PGS elastomers increased cell alignment, calcium transient homogeneity and cell connectivity. The intensity of the calcium transients in cardiomyocytes was enhanced when cultured on PGS which released a small molecule BDNF mimetic. This study demonstrates that robust micropatterned elastomer films are a potential candidate for the delivery of functional cardiomyocytes and factors to the injured or dysfunctional myocardium, as well as providing novel in vitro platforms to study cardiomyocyte physiology.

AB - Myocardial tissue engineering is a promising therapy for myocardial infarction recovery. The success of myocardial tissue engineering is likely to rely on the combination of cardiomyocytes, pro-survival regulatory signals, and a flexible biomaterial structure that can deliver them. In this study, poly (glycerol sebacate) (PGS), which exhibits stable elasticity under repeated tensile loading, was engineered to provide physical features that aligned cardiomyocytes in a similar manner to that seen in native cardiac tissue. In addition, a small molecule mimetic of brain derived neurotrophic factor (BDNF) was polymerised into the PGS to achieve a continuous and steady release. Micropatterning of PGS elastomers increased cell alignment, calcium transient homogeneity and cell connectivity. The intensity of the calcium transients in cardiomyocytes was enhanced when cultured on PGS which released a small molecule BDNF mimetic. This study demonstrates that robust micropatterned elastomer films are a potential candidate for the delivery of functional cardiomyocytes and factors to the injured or dysfunctional myocardium, as well as providing novel in vitro platforms to study cardiomyocyte physiology.

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U2 - 10.1021/acsbiomaterials.8b00084

DO - 10.1021/acsbiomaterials.8b00084

M3 - Article

VL - 4

SP - 2494

EP - 2504

JO - ACS Biomaterials Science and Engineering

JF - ACS Biomaterials Science and Engineering

SN - 2373-9878

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