Micro-structurally detailed model of a therapeutic hydrogel injectate in a rat biventricular cardiac geometry for computational simulations

Abstract

Biomaterial injection-based therapies have showed cautious success in restoration of cardiac function and prevention of adverse remodelling into heart failure after myocardial infarction (MI). However, the underlying mechanisms are not well understood. Computational studies utilised simplified representations of the therapeutic myocardial injectates. Wistar rats underwent experimental infarction followed by immediate injection of polyethylene glycol hydrogel in the infarct region. Hearts were explanted, cryo-sectioned and the region with the injectate histologically analysed. Histological micrographs were used to reconstruct the dispersed hydrogel injectate. Cardiac magnetic resonance imaging data from a healthy rat were used to obtain an end-diastolic biventricular geometry which was subsequently adjusted and combined with the injectate model. The computational geometry of the injectate exhibited microscopic structural details found the in situ. The combination of injectate and cardiac geometry provides realistic geometries for multiscale computational studies of intra-myocardial injectate therapies for the rat model that has been widely used for MI research.

Keywords::

• myocardial infarction
• therapeutic injectate
• image-based reconstruction
• computational modelling
• hydrogel

Acknowledgements

This study was supported financially, in part, by the National Research Foundation (NRF) of South Africa, the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa, the Medical Research Council of South Africa, and NIH Grant No. R21AA017410. Any opinion, findings and conclusions or recommendations expressed in this publication are those of the authors and therefore the NRF does not accept any liability in regard thereto. MSS acknowledges the International Society of Biomechanics Matching Dissertation Grant.

Conflict of interest statement: The authors declare that they have no conflicts of interest in connection with the work presented in this manuscript.