Investigation of the effect of injected hydrogel properties on post-myocardial infarction ventricular remodeling using an integrated experimental-numerical finite element modeling approach

项目概要/摘要 心力衰竭（HF）是世界范围内死亡的主要原因之一，由左心室的不良重塑引起。 心肌梗死（MI）后心脏的心室（LV）。为了改善LV重构，已经表明， 通过直接注射生物材料的梗死修饰具有限制梗死扩展的潜力。 然而，几乎没有努力针对确定的最佳的物理特性， 注射液，其与梗死心肌的相互作用，以及患者特异性几何图案的影响， 注射注射的基于HA的水凝胶减少梗塞扩展和改善不利的后梗塞的能力被证实。 MI重塑取决于HA水凝胶性质（弹性模量、降解速率和分布）。 最佳材料的设计及其部署可以使用器官级模型在计算机上完成 心肌梗死后左心室重塑，从而允许开发优化的材料， 和临床实验。拟议的工作采用了一种新的可调透明质酸（HA）为基础的 可注射材料和临床相关绵羊梗塞模型。最先进的磁共振成像技术 方法，结合实验确定的3D梗死材料属性，作为输入， 用于评估健康、梗死和注射的LV几何形状和微结构的有限元模型 心肌该方法的使用将产生能够忠实预测的更准确的模型。 注射治疗对心肌梗死后组织和器官水平事件的影响，允许患者发生 MI的特异性治疗和患者结局的改善。

PROJECT SUMMARY/ABSTRACT Heart failure (HF), one of the leading causes of death worldwide, results from adverse remodeling of the left ventricle (LV) of the heart after myocardial infarction (MI). To ameliorate LV remodeling, it has been shown that infarction modification through direct injection of biomaterials has the potential to limit infarct expansion. However, little effort has been directed toward determination of the optimal physical characteristics of the injectate, its interaction with infarcted myocardium, and the effect of patient-specific geometric patterns of injection. The ability of injected HA-based hydrogels to reduce infarct expansion and ameliorate adverse post- MI remodeling is dependent on HA hydrogel properties (elastic modulus, degradation rate, and distribution). The design of optimal materials and their deployment can be accomplished in-silico using organ-level models of the post-MI remodeling LV, thus allowing optimized materials to be developed with a limited need for animal and clinical experimentation. The proposed work employs a novel tunable hyaluronic acid (HA)-based injectable material and a clinically relevant ovine infarct model. State-of-the-art magnetic resonance imaging methodologies, combined with experimentally determined 3D infarct material properties, serve as input for a finite element model for assessing LV geometry and microstructure of healthy, infarcted, and injected myocardium. Use of the approach will yield substantially more accurate models capable of faithful prediction of injection therapies’ impact on tissue- and organ-level events post-MI, allowing for the development of patient- specific therapies for MI and improvement of patient outcomes.