Evaluation of a polyurethane-reinforced hydrogel patch in a rat right ventricle wall replacement model.

ABSTRACT

Congenital heart defects affect about 1% births in the United States. Many of the defects are treated with surgically implanted patches made from inactive materials or fixed pericardium that do not grow with the patients, leading to an increased risk of arrhythmia, sudden cardiac death, and heart failure. This study investigated an angiogenic poly(ethylene glycol) fibrin-based hydrogel reinforced with an electrospun biodegradable poly(ether ester urethane) urea (BPUR) mesh layer that was designed to encourage cell invasion, angiogenesis, and regenerative remodeling in the repair of an artificial defect created onto the rat right ventricle wall. Electrocardiogram signals were analyzed, heart function was measured, and fibrosis, macrophage infiltration, muscularization, vascularization, and defect size were evaluated at 4- and 8-weeks post-surgery. Compared with rats with fixed pericardium patches, rats with BPUR-reinforced hydrogel patches had fewer arrhythmias and greater right ventricular ejection fraction and cardiac output, as well as greater left ventricular ejection fraction, fractional shorting, stroke work and cardiac output. Histology and immunofluorescence staining showed less fibrosis and less patch material remaining in rats with BPUR-reinforced hydrogel patches at 4- and 8-weeks. Rats with BPUR-reinforced hydrogel patches also had a greater volume of granular tissue, a greater volume of muscularized tissue, more blood vessels, and a greater number of leukocytes, pan-macrophages, and M2 macrophages at 8 weeks. Overall, this study demonstrated that the engineered BPUR-reinforced hydrogel patch initiated greater regenerative vascular and muscular remodeling with a limited fibrotic response, resulting in fewer incidences of arrhythmia and improved heart function compared with fixed pericardium patches when applied to heal the defects created on the rat right ventricle wall. STATEMENT OF SIGNIFICANCE: The study tested a polyurethane-reinforced hydrogel patch in a rat right ventricle wall replacement model. Compared with fixed pericardium patches, these reinforced hydrogel patches initiated greater regenerative vascular and muscular remodeling with a reduced fibrotic response, resulting in fewer incidences of arrhythmia and improved heart function at 4- and 8-weeks post surgery. Overall, the new BPUR-reinforced hydrogel patches resulted in better heart function when replacing contractile myocardium than fixed pericardium patches.