Biology subjects

Sirry, M. S.

Publications and source records attributed to Sirry, M. S..

3 recordsLinked to original sources

bioRxiv2023

In silico mechanics and TGF-β expression of stem cells intramyocardially transplanted with a biomaterial injectate for treatment of myocardial infarction

PurposeBiomaterial and stem cell delivery are promising approaches to treating myocardial infarction. However, the mechanical and biochemical mechanisms underlying the therapeutic benefits require further clarification. This study aimed to assess the deformation of stem cells injected with the biomaterial into the infarcted heart. MethodsA microstructural finite element model of a mid-wall infarcted myocardial region was developed from ex vivo microcomputed tomography data of a rat heart with left ventricular infarct and intramyocardial biomaterial injectate. Nine cells were numerically seeded in the injectate of the microstructural model. The microstructural and a previously developed biventricular finite element model of the same rat heart were used to quantify the deformation of the cells during a cardiac cycle for a biomaterial elastic modulus (Einj) ranging between 4.1 and 405,900 kPa. ResultsThe transplanted cells deformation was largest for Einj = 7.4 kPa, matching that of the cells, and decreased for an increase and decrease in Einj. The cell deformation was more sensitive to Einj changes for softer (Einj [≤] 738 kPa) than stiffer biomaterials. ConclusionsCombining the microstructural and biventricular finite element models enables quantifying micromechanics and signalling of transplanted cells in the heart. The approach offers a broader scope for in silico investigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.

bioengineering↗

bioRxiv2022

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 one 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 3,852 mm-3 in the injectate region due to the microstructural intramyocardial dispersion. Parametric simulations were conducted with the injectates 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.

biophysics↗

bioRxiv2019

Identification of orthotropic material parameters for acute, necrotic, fibrotic and remodelling myocardial infarcts in the rat

Finite element (FE) models have been effectively utilized in studying biomechanical aspects of myocardial infarction (MI). Although the rat is a widely used animal model for MI, there is a lack of material parameters based on anisotropic constitutive models for rat myocardial infarcts in literature. This study aimed at employing inverse methods to identify the parameters of an orthotropic constitutive model for myocardial infarcts in the acute, necrotic, fibrotic and remodelling phases utilizing the biaxial mechanical data developed in a previous study. FE model was developed mimicking the setup of the biaxial tensile experiment. The orthotropic case of the generalized Fung constitutive model was utilized to model the material properties of the infarct. The parameters of Fung model were optimized so that the FE solution best fitted the biaxial experimental stress-strain data. A genetic algorithm was used to minimize the objective function. Fung orthotropic material parameters for different infarct stages were identified. The FE model predictions best approximated the experimental data of the 28 days infarct stage with 3.0% mean absolute percentage error. The worst approximation was for the 7 days stage with 3.6% error. This study demonstrated that the experimental biaxial stress-strain data of healing rat infarcts could be successfully approximated using inverse FE methods and genetic algorithms. The material parameters identified in this study will provide an essential platform for FE investigations of biomechanical aspects of MI and the development of therapies.

bioengineering↗