? DESCRIPTION: Structural, congenital heart defects are the number one non-infectious cause of infant death in the US. Repair often requires multiple surgeries and implantation of nonviable or mechanically inactive patches, which are non-functional but occupy areas important to heart function. These patches are highly effective in the short- term, but as the infant grows and the patches remain static they can cause arrhythmias, decreased cardiac output, and an increased likelihood of sudden cardiac death in addition to the possibility of calcification or aneurysm formation necessitating further surgery. The overarching goal of this study is to create a biodegradable patch prevascularized with cells harvested from amniotic fluid that is autologous for repair in a newborn, can recruit resident progenitor cells from the infant's heart and eventually be absorbed and become functional heart tissue. Current patch materials are made from Dacron, Teflon or fixed pericardium, which have been shown to lead to a foreign body reaction, resulting in a large, scar-like capsule in the heart. We recently published on a biodegradable cardiac patch that is strong enough to be sutured into a ventricle as a full-thickness patch, and has a porous structure that is rapidly populated by cardiac cells. In the proposed study, we will create multi-layered bio-synthetic patches with strong supporting cores of polyurethane, and cell-friendly fibrin modified with poly(ethylene glycol) to control degradatio and inflammatory response. We will then investigate these materials in vitro in cultures with cardiomyocytes. Finally, we will assess the functionality in vivo in a right ventricle free wall replacement in a nude rat model, and assess vasculature function, cell survival and heart function. If successful, these studies will develop a method for generating a full thickness myocardial patch for repair of congenital heart defects. This therapeutic option could transform the surgical approach to major congenital heart defects.

R01HL130436

2016-01-20

2021-05-31