Effect of biomaterial stiffness on cardiac mechanics in a biventricular infarcted rat heart model with microstructural representation of in situ intramyocardial injectate
Effect of biomaterial stiffness on cardiac mechanics in a biventricular infarcted rat heart model with microstructural representation of in situ intramyocardial injectate
Intramyocardial delivery of biomaterials is a promising concept for treating myocardial infarction. The delivered biomaterial provides mechanical support and attenuates wall thinning and elevated wall stress in the infarct region. This study aimed at developing a biventricular finite element model of an infarcted rat heart with a microstructural representation of an in situ biomaterial injectate, and a parametric investigation of the effect of the injectate stiffness on the cardiac mechanics. A three-dimensional subject-specific biventricular finite element model of a rat heart with left ventricular infarct and microstructurally dispersed biomaterial delivered 1 week after infarct induction was developed from ex vivo microcomputed tomography data. The volumetric mesh density varied between 303 mm−3 in the myocardium and 3852 mm−3 in the injectate region due to the microstructural intramyocardial dispersion. Parametric simulations were conducted with the injectate's elastic modulus varying from 4.1 to 405,900 kPa, and myocardial and injectate strains were recorded. With increasing injectate stiffness, the end-diastolic median myocardial fibre and cross-fibre strain decreased in magnitude from 3.6% to 1.1% and from −6.0% to −2.9%, respectively. At end-systole, the myocardial fibre and cross-fibre strain decreased in magnitude from −20.4% to −11.8% and from 6.5% to 4.6%, respectively. In the injectate, the maximum and minimum principal strains decreased in magnitude from 5.4% to 0.001% and from −5.4% to −0.001%, respectively, at end-diastole and from 38.5% to 0.06% and from −39.0% to −0.06%, respectively, at end-systole. With the microstructural injectate geometry, the developed subject-specific cardiac finite element model offers potential for extension to cellular injectates and in silico studies of mechanotransduction and therapeutic signalling in the infarcted heart with an infarct animal model extensively used in preclinical research.
biomaterial injection therapy, cardiac mechanics, finite element method, myocardial infarction
Motchon, Y.D.
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Sack, Kevin L.
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Sirry, M.S.
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Kruger, M.
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Pauwels, E.
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Van Loo, D.
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De Muynck, A.
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Van Hoorebeke, L
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Davies, Neil H.
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Franz, Thomas
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Motchon, Y.D.
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Sack, Kevin L.
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Sirry, M.S.
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Kruger, M.
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Pauwels, E.
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Van Loo, D.
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De Muynck, A.
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Van Hoorebeke, L
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Davies, Neil H.
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Franz, Thomas
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Motchon, Y.D., Sack, Kevin L., Sirry, M.S., Kruger, M., Pauwels, E., Van Loo, D., De Muynck, A., Van Hoorebeke, L, Davies, Neil H. and Franz, Thomas
(2023)
Effect of biomaterial stiffness on cardiac mechanics in a biventricular infarcted rat heart model with microstructural representation of in situ intramyocardial injectate.
International Journal for Numerical Methods in Biomedical Engineering, 39 (5), [e3693].
(doi:10.1002/cnm.3693).
Abstract
Intramyocardial delivery of biomaterials is a promising concept for treating myocardial infarction. The delivered biomaterial provides mechanical support and attenuates wall thinning and elevated wall stress in the infarct region. This study aimed at developing a biventricular finite element model of an infarcted rat heart with a microstructural representation of an in situ biomaterial injectate, and a parametric investigation of the effect of the injectate stiffness on the cardiac mechanics. A three-dimensional subject-specific biventricular finite element model of a rat heart with left ventricular infarct and microstructurally dispersed biomaterial delivered 1 week after infarct induction was developed from ex vivo microcomputed tomography data. The volumetric mesh density varied between 303 mm−3 in the myocardium and 3852 mm−3 in the injectate region due to the microstructural intramyocardial dispersion. Parametric simulations were conducted with the injectate's elastic modulus varying from 4.1 to 405,900 kPa, and myocardial and injectate strains were recorded. With increasing injectate stiffness, the end-diastolic median myocardial fibre and cross-fibre strain decreased in magnitude from 3.6% to 1.1% and from −6.0% to −2.9%, respectively. At end-systole, the myocardial fibre and cross-fibre strain decreased in magnitude from −20.4% to −11.8% and from 6.5% to 4.6%, respectively. In the injectate, the maximum and minimum principal strains decreased in magnitude from 5.4% to 0.001% and from −5.4% to −0.001%, respectively, at end-diastole and from 38.5% to 0.06% and from −39.0% to −0.06%, respectively, at end-systole. With the microstructural injectate geometry, the developed subject-specific cardiac finite element model offers potential for extension to cellular injectates and in silico studies of mechanotransduction and therapeutic signalling in the infarcted heart with an infarct animal model extensively used in preclinical research.
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Numer Methods Biomed Eng - 2023 - Motchon - Effect of biomaterial stiffness on cardiac mechanics in a biventricular
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Accepted/In Press date: 29 January 2023
e-pub ahead of print date: 2 March 2023
Additional Information:
Funding Information:
This work was supported by financially supported by the National Research Foundation of South Africa (IFR14011761118 to TF), the South African Medical Research Council (SIR328148 to TF), and the CSIR Centre for High Performance Computing (CHPC Flagship Project Grant IRMA9543 to TF), and the Dr. Leopold und Carmen Ellinger Stiftung (UCT Three‐Way PhD Global Partnership Programme Grant DAD937134 to TF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Any opinion, findings, conclusions, and recommendations expressed in this publication are those of the authors, and therefore, the funders do not accept any liability.
Funding Information:
National Research Foundation of South Africa, Grant/Award Number: IFR14011761118; South African Medical Research Council, Grant/Award Number: SIR328148; CSIR Centre for High Performance Computing, Grant/Award Number: IRMA9543; Dr. Leopold und Carmen Ellinger Stiftung, Grant/Award Number: DAD937134 Funding information
Publisher Copyright:
© 2023 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.
Keywords:
biomaterial injection therapy, cardiac mechanics, finite element method, myocardial infarction
Identifiers
Local EPrints ID: 484632
URI: http://eprints.soton.ac.uk/id/eprint/484632
ISSN: 2040-7947
PURE UUID: ac830553-0b1d-416a-9870-23e326ee5697
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Date deposited: 17 Nov 2023 18:11
Last modified: 17 Mar 2024 01:52
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Contributors
Author:
Y.D. Motchon
Author:
Kevin L. Sack
Author:
M.S. Sirry
Author:
M. Kruger
Author:
E. Pauwels
Author:
D. Van Loo
Author:
A. De Muynck
Author:
L Van Hoorebeke
Author:
Neil H. Davies
Author:
Thomas Franz
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