A Preliminary Computational Investigation Into the Flow of PEG in Rat Myocardial Tissue for Regenerative Therapy

Front Cardiovasc Med. 2019 Aug 7:6:104. doi: 10.3389/fcvm.2019.00104. eCollection 2019.

Abstract

Myocardial infarction (MI), a type of cardiovascular disease, affects a significant proportion of people around the world. Traditionally, non-communicable chronic diseases were largely associated with aging populations in higher income countries. It is now evident that low- to middle-income countries are also affected and in these settings, younger individuals are at high risk. Currently, interventions for MI prolong the time to heart failure. Regenerative medicine and stem cell therapy have the potential to mitigate the effects of MI and to significantly improve the quality of life for patients. The main drawback with these therapies is that many of the injected cells are lost due to the vigorous motion of the heart. Great effort has been directed toward the development of scaffolds which can be injected alongside stem cells, in an attempt to improve retention and cell engraftment. In some cases, the scaffold alone has been seen to improve heart function. This study focuses on a synthetic polyethylene glycol (PEG) based hydrogel which is injected into the heart to improve left ventricular function following MI. Many studies in literature characterize PEG as a Newtonian fluid within a specified shear rate range, on the macroscale. The aim of the study is to characterize the flow of a 20 kDa PEG on the microscale, where the behavior is likely to deviate from macroscale flow patterns. Micro particle image velocimetry (μPIV) is used to observe flow behavior in microchannels, representing the gaps in myocardial tissue. The fluid exhibits non-Newtonian, shear-thinning behavior at this scale. Idealized two-dimensional computational fluid dynamics (CFD) models of PEG flow in microchannels are then developed and validated using the μPIV study. The validated computational model is applied to a realistic, microscopy-derived myocardial tissue model. From the realistic tissue reconstruction, it is evident that the myocardial flow region plays an important role in the distribution of PEG, and therefore, in the retention of material.

Keywords: computational fluid dynamics; injectate therapy; myocardial infarction; particle image velocimetry; polyethylene glycol hydrogel; retention.