capillary-force-lithography-for-cardiac-tissue-engineering

Capillary Force Lithography for Cardiac Tissue Engineering

Cardiovascular disease remains the leading cause of death worldwide1. Cardiac tissue engineering holds much promise to deliver groundbreaking medical ...

preclinical-drug-testing-in-scalable-3d-engineered-muscle-tissues

Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues

Accurately modeling healthy and disease conditions in vitro is vital for the development of new treatment strategies and therapeutics. For cardiac and ...

University of Washington

Curi Bio Inc.

The mechanical properties of healing myocardial infarcts are a critical determinant of pump function and the transition to heart failure. Recent reports suggest that modifying infarct mechanical properties can improve function and limit ventricular remodeling. However, little attempt has been made to identify the specific infarct material properties that would optimize left ventricular (LV) function. We utilized a finite-element model of a large anteroapical infarct in a dog heart to explore a wide range of infarct mechanical properties. Isotropic stiffening of the infarct reduced end-diastolic (EDV) and end-systolic (ESV) volumes, improved LV contractility, but had little effect on stroke volume. A highly anisotropic infarct, with high longitudinal stiffness but low circumferential stiffness coefficients, produced the best stroke volume by increasing diastolic filling, without affecting contractility or ESV. Simulated infarcts in two different locations displayed different transmural strain patterns. Our results suggest that there is a general trade-off between acutely reducing LV size and acutely improving LV pump function, that isotropically stiffening the infarct is not the only option of potential therapeutic interest, and that customizing therapies for different infarct locations may be important. Our model results should provide guidance for design and development of therapies to improve LV function by modifying infarct mechanical properties.

Model-based design of mechanical therapies for myocardial infarction.

An emerging therapy to limit adverse heart remodelling following myocardial infarction (MI) is the injection of polymers into the infarcted left ventricle (LV). In the few numerical studies carried out in this field, the definition and distribution of the hydrogel in the infarcted myocardium were simplified. In this computational study, a more realistic biomaterial distribution was simulated after which the effect on cardiac function and mechanics was studied. A validated finite element heart model was used in which an antero-apical infarct was defined. Four infarct models were created representing different temporal phases in the progression of a MI. Hydrogel layers were simulated in the infarcted myocardium in each model. Biomechanical and functional improvement of the LV was found after hydrogel inclusion in the ischaemic models representing the early phases of MI. In contrast, only functional but no mechanical restitution was shown in the scar model due to hydrogel presence.

Jesse Macadangdang

Department of Bioengineering

University of Washington

Capillary Force Lithography for Cardiac Tissue Engineering

Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues

Jesse Macadangdang

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Bioengineering

University of Washington

Capillary Force Lithography for Cardiac Tissue Engineering

Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues

Department of Bioengineering