A nanopatterned cell-seeded cardiac patch prevents electro-uncoupling and improves the therapeutic efficacy of cardiac repair

Yi Dong Lin, Ming Chin Ko, Su Ting Wu, Sheng Feng Li, Jung Feng Hu, Yu Jun Lai, Hans I.Chen Harn, I. Chuang Laio, Ming Long Yeh, Hung I. Yeh, Ming Jer Tang, Kung Chao Chang, Fong Chin Su, Erika I.H. Wei, Sho Tone Lee, Jyh Hong Chen, Allan S. Hoffman, Wen Teng Wu, Patrick C.H. Hsieh

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The heart is an extremely sophisticated organ with nanoscale anisotropic structure, contractility and electro-conductivity; however, few studies have addressed the influence of cardiac anisotropy on cell transplantation for myocardial repair. Here, we hypothesized that a graft's anisotropy of myofiber orientation determines the mechano-electrical characteristics and the therapeutic efficacy. We developed aligned- and random-orientated nanofibrous electrospun patches (aEP and rEP, respectively) with or without seeding of cardiomyocytes (CMs) and endothelial cells (ECs) to test this hypothesis. Atomic force microscopy showed a better beating frequency and amplitude of CMs when cultured on aEP than that from cells cultured on rEP. For the in vivo test, a total of 66 rats were divided into six groups: sham, myocardial infarction (MI), MI + aEP, MI + rEP, MI + CM-EC/aEP and MI + CM-EC/rEP (n ≥ 10 for each group). Implantation of aEP or rEP provided mechanical support and thus retarded functional aggravation at 56 days after MI. Importantly, CM-EC/aEP implantation further improved therapeutic outcomes, while cardiac deterioration occurred on the CM-EC/rEP group. Similar results were shown by hemodynamic and infarct size examination. Another independent in vivo study was performed and electrocardiography and optical mapping demonstrated that there were more ectopic activities and defective electro-coupling after CM-EC/rEP implantation, which worsened cardiac functions. Together these results provide comprehensive functional characterizations and demonstrate the therapeutic efficacy of a nanopatterned anisotropic cardiac patch. Importantly, the study confirms the significance of cardiac anisotropy recapitulation in myocardial tissue engineering, which is valuable for the future development of translational nanomedicine.

Original languageEnglish
Pages (from-to)567-580
Number of pages14
JournalBiomaterials Science
Volume2
Issue number4
DOIs
Publication statusPublished - 2014 Apr

Fingerprint

Endothelial cells
Repair
Anisotropy
Medical nanotechnology
Hemodynamics
Electrocardiography
Tissue engineering
Grafts
Deterioration
Rats
Atomic force microscopy

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Materials Science(all)

Cite this

Lin, Yi Dong ; Ko, Ming Chin ; Wu, Su Ting ; Li, Sheng Feng ; Hu, Jung Feng ; Lai, Yu Jun ; Harn, Hans I.Chen ; Laio, I. Chuang ; Yeh, Ming Long ; Yeh, Hung I. ; Tang, Ming Jer ; Chang, Kung Chao ; Su, Fong Chin ; Wei, Erika I.H. ; Lee, Sho Tone ; Chen, Jyh Hong ; Hoffman, Allan S. ; Wu, Wen Teng ; Hsieh, Patrick C.H. / A nanopatterned cell-seeded cardiac patch prevents electro-uncoupling and improves the therapeutic efficacy of cardiac repair. In: Biomaterials Science. 2014 ; Vol. 2, No. 4. pp. 567-580.
@article{a7ac8269d5a244008b26f80688ac85fd,
title = "A nanopatterned cell-seeded cardiac patch prevents electro-uncoupling and improves the therapeutic efficacy of cardiac repair",
abstract = "The heart is an extremely sophisticated organ with nanoscale anisotropic structure, contractility and electro-conductivity; however, few studies have addressed the influence of cardiac anisotropy on cell transplantation for myocardial repair. Here, we hypothesized that a graft's anisotropy of myofiber orientation determines the mechano-electrical characteristics and the therapeutic efficacy. We developed aligned- and random-orientated nanofibrous electrospun patches (aEP and rEP, respectively) with or without seeding of cardiomyocytes (CMs) and endothelial cells (ECs) to test this hypothesis. Atomic force microscopy showed a better beating frequency and amplitude of CMs when cultured on aEP than that from cells cultured on rEP. For the in vivo test, a total of 66 rats were divided into six groups: sham, myocardial infarction (MI), MI + aEP, MI + rEP, MI + CM-EC/aEP and MI + CM-EC/rEP (n ≥ 10 for each group). Implantation of aEP or rEP provided mechanical support and thus retarded functional aggravation at 56 days after MI. Importantly, CM-EC/aEP implantation further improved therapeutic outcomes, while cardiac deterioration occurred on the CM-EC/rEP group. Similar results were shown by hemodynamic and infarct size examination. Another independent in vivo study was performed and electrocardiography and optical mapping demonstrated that there were more ectopic activities and defective electro-coupling after CM-EC/rEP implantation, which worsened cardiac functions. Together these results provide comprehensive functional characterizations and demonstrate the therapeutic efficacy of a nanopatterned anisotropic cardiac patch. Importantly, the study confirms the significance of cardiac anisotropy recapitulation in myocardial tissue engineering, which is valuable for the future development of translational nanomedicine.",
author = "Lin, {Yi Dong} and Ko, {Ming Chin} and Wu, {Su Ting} and Li, {Sheng Feng} and Hu, {Jung Feng} and Lai, {Yu Jun} and Harn, {Hans I.Chen} and Laio, {I. Chuang} and Yeh, {Ming Long} and Yeh, {Hung I.} and Tang, {Ming Jer} and Chang, {Kung Chao} and Su, {Fong Chin} and Wei, {Erika I.H.} and Lee, {Sho Tone} and Chen, {Jyh Hong} and Hoffman, {Allan S.} and Wu, {Wen Teng} and Hsieh, {Patrick C.H.}",
year = "2014",
month = "4",
doi = "10.1039/c3bm60289c",
language = "English",
volume = "2",
pages = "567--580",
journal = "Biomaterials Science",
issn = "2047-4830",
publisher = "Royal Society of Chemistry",
number = "4",

}

Lin, YD, Ko, MC, Wu, ST, Li, SF, Hu, JF, Lai, YJ, Harn, HIC, Laio, IC, Yeh, ML, Yeh, HI, Tang, MJ, Chang, KC, Su, FC, Wei, EIH, Lee, ST, Chen, JH, Hoffman, AS, Wu, WT & Hsieh, PCH 2014, 'A nanopatterned cell-seeded cardiac patch prevents electro-uncoupling and improves the therapeutic efficacy of cardiac repair', Biomaterials Science, vol. 2, no. 4, pp. 567-580. https://doi.org/10.1039/c3bm60289c

A nanopatterned cell-seeded cardiac patch prevents electro-uncoupling and improves the therapeutic efficacy of cardiac repair. / Lin, Yi Dong; Ko, Ming Chin; Wu, Su Ting; Li, Sheng Feng; Hu, Jung Feng; Lai, Yu Jun; Harn, Hans I.Chen; Laio, I. Chuang; Yeh, Ming Long; Yeh, Hung I.; Tang, Ming Jer; Chang, Kung Chao; Su, Fong Chin; Wei, Erika I.H.; Lee, Sho Tone; Chen, Jyh Hong; Hoffman, Allan S.; Wu, Wen Teng; Hsieh, Patrick C.H.

In: Biomaterials Science, Vol. 2, No. 4, 04.2014, p. 567-580.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A nanopatterned cell-seeded cardiac patch prevents electro-uncoupling and improves the therapeutic efficacy of cardiac repair

AU - Lin, Yi Dong

AU - Ko, Ming Chin

AU - Wu, Su Ting

AU - Li, Sheng Feng

AU - Hu, Jung Feng

AU - Lai, Yu Jun

AU - Harn, Hans I.Chen

AU - Laio, I. Chuang

AU - Yeh, Ming Long

AU - Yeh, Hung I.

AU - Tang, Ming Jer

AU - Chang, Kung Chao

AU - Su, Fong Chin

AU - Wei, Erika I.H.

AU - Lee, Sho Tone

AU - Chen, Jyh Hong

AU - Hoffman, Allan S.

AU - Wu, Wen Teng

AU - Hsieh, Patrick C.H.

PY - 2014/4

Y1 - 2014/4

N2 - The heart is an extremely sophisticated organ with nanoscale anisotropic structure, contractility and electro-conductivity; however, few studies have addressed the influence of cardiac anisotropy on cell transplantation for myocardial repair. Here, we hypothesized that a graft's anisotropy of myofiber orientation determines the mechano-electrical characteristics and the therapeutic efficacy. We developed aligned- and random-orientated nanofibrous electrospun patches (aEP and rEP, respectively) with or without seeding of cardiomyocytes (CMs) and endothelial cells (ECs) to test this hypothesis. Atomic force microscopy showed a better beating frequency and amplitude of CMs when cultured on aEP than that from cells cultured on rEP. For the in vivo test, a total of 66 rats were divided into six groups: sham, myocardial infarction (MI), MI + aEP, MI + rEP, MI + CM-EC/aEP and MI + CM-EC/rEP (n ≥ 10 for each group). Implantation of aEP or rEP provided mechanical support and thus retarded functional aggravation at 56 days after MI. Importantly, CM-EC/aEP implantation further improved therapeutic outcomes, while cardiac deterioration occurred on the CM-EC/rEP group. Similar results were shown by hemodynamic and infarct size examination. Another independent in vivo study was performed and electrocardiography and optical mapping demonstrated that there were more ectopic activities and defective electro-coupling after CM-EC/rEP implantation, which worsened cardiac functions. Together these results provide comprehensive functional characterizations and demonstrate the therapeutic efficacy of a nanopatterned anisotropic cardiac patch. Importantly, the study confirms the significance of cardiac anisotropy recapitulation in myocardial tissue engineering, which is valuable for the future development of translational nanomedicine.

AB - The heart is an extremely sophisticated organ with nanoscale anisotropic structure, contractility and electro-conductivity; however, few studies have addressed the influence of cardiac anisotropy on cell transplantation for myocardial repair. Here, we hypothesized that a graft's anisotropy of myofiber orientation determines the mechano-electrical characteristics and the therapeutic efficacy. We developed aligned- and random-orientated nanofibrous electrospun patches (aEP and rEP, respectively) with or without seeding of cardiomyocytes (CMs) and endothelial cells (ECs) to test this hypothesis. Atomic force microscopy showed a better beating frequency and amplitude of CMs when cultured on aEP than that from cells cultured on rEP. For the in vivo test, a total of 66 rats were divided into six groups: sham, myocardial infarction (MI), MI + aEP, MI + rEP, MI + CM-EC/aEP and MI + CM-EC/rEP (n ≥ 10 for each group). Implantation of aEP or rEP provided mechanical support and thus retarded functional aggravation at 56 days after MI. Importantly, CM-EC/aEP implantation further improved therapeutic outcomes, while cardiac deterioration occurred on the CM-EC/rEP group. Similar results were shown by hemodynamic and infarct size examination. Another independent in vivo study was performed and electrocardiography and optical mapping demonstrated that there were more ectopic activities and defective electro-coupling after CM-EC/rEP implantation, which worsened cardiac functions. Together these results provide comprehensive functional characterizations and demonstrate the therapeutic efficacy of a nanopatterned anisotropic cardiac patch. Importantly, the study confirms the significance of cardiac anisotropy recapitulation in myocardial tissue engineering, which is valuable for the future development of translational nanomedicine.

UR - http://www.scopus.com/inward/record.url?scp=84895793474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895793474&partnerID=8YFLogxK

U2 - 10.1039/c3bm60289c

DO - 10.1039/c3bm60289c

M3 - Article

AN - SCOPUS:84895793474

VL - 2

SP - 567

EP - 580

JO - Biomaterials Science

JF - Biomaterials Science

SN - 2047-4830

IS - 4

ER -