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

Motchon, Y. D.; Sack, K. L.; Sirry, M. S.; Nchejane, N. J.; Abdalrahman, T.; Nagawa, J.; Kruger, M.; Pauwels, E.; Van Loo, D.; De Muynck, A.; Van Hoorebeke, L.; Davies, N. H.; Franz, T.

doi:10.1101/2023.05.10.540185

bioRxiv · 10.1101/2023.05.10.540185

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

Motchon, Y. D.·Sack, K. L.·Sirry, M. S.·Nchejane, N. J.·Abdalrahman, T.·Nagawa, J.·Kruger, M.·Pauwels, E.·Van Loo, D.·De Muynck, A.·Van Hoorebeke, L.·Davies, N. H.·Franz, T.

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Abstract

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.

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Motchon, Y. D., Sack, K. L., Sirry, M. S., Nchejane, N. J., Abdalrahman, T., Nagawa, J., Kruger, M., Pauwels, E., Van Loo, D., De Muynck, A., Van Hoorebeke, L., Davies, N. H., Franz, T.. 2023-05-12. In silico mechanics and TGF-β expression of stem cells intramyocardially transplanted with a biomaterial injectate for treatment of myocardial infarction. https://doi.org/10.1101/2023.05.10.540185

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