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

项目摘要/摘要 心力衰竭(HF)是世界范围内主要的死亡原因之一，其原因是左心室的不良重塑。 心肌梗死(MI)后的心脏(LV)。为了改善左室重构，已经证明 通过直接注射生物材料来修饰梗塞具有限制梗塞扩大的潜力。 然而，几乎没有针对确定最优物理特性的努力 注射剂、其与梗死心肌的相互作用以及患者特定几何图形的影响 注射。注射羟基磷灰石水凝胶减少脑梗塞扩大和改善术后不良反应的能力 MI重塑取决于HA水凝胶的性质(弹性模数、降解率和分布)。 最优材料的设计和它们的部署可以使用器官级别的模型在硅中完成 心肌梗死后左室重塑，从而允许在动物需求有限的情况下开发优化材料 和临床实验。提出的工作采用了一种新型的可调透明质酸(HA)为基础 可注射材料和临床相关的绵羊梗塞模型。最先进的磁共振成像技术 方法学，结合实验确定的3D梗塞材料特性，作为输入 评价健康、梗死和注射后左室几何结构和微结构的有限元模型 心肌。该方法的使用将产生更准确的模型，能够忠实地预测 注射疗法对心肌梗死后组织和器官水平事件的影响，使患者- 针对心肌梗塞和改善患者预后的特定治疗方法。

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.