Mending the heart: cardiac remodeling using a combinatorial biomimetic poly(glycerol sebacate)/poly(caprolactone) patch

摘要

Introduction: Congenital heart defects (CHDs) affect over one million Americans and increase the risk of developing several cardiovascular complications. Most of the synthetic cardiac patches currently available for repairing or reconstructing CHD are nonviable, non-contractile, lack regenerative capability, and do not grow as the children develop. To address this challenge, we therefore designed and fabricated a combinatorial biomimetic cardiac patches made from a fast-degrading elastic polymer with a slow-degrading outer shell: a poly(glycerol sebacate) (PGS) microporous scaffold reinforced with electrospun poly(carprolactone) (PCL) nanoflbers on outer surface. A similar combinatorial scaffold has been proven a biomimetic and remolded into neo arteries with the similar gross appearance to the native rat aortas when transplanted into rats. This study is to evaluate the performance of PGS/PCL patches for the right ventricular reconstruction and cardiac tissue engineering. Materials and Methods: A PGS/PCL combinatorial patch was used to reconstruct a right ventricular outflow tract (RVOT) defect in a Sprague Dawley rat model with the end points of remodeling function at 4,8 and 16 weeks. Control rats were implanted with Gortex expanded polytetrafluoroethylene (ePTFE) with an end of point at 16 weeks. Histologic evaluation was performed at 4,8, and 16 weeks post-surgery; cardiac function was assessed by echocardiographyat 4,8, and 16 weeks post-surgery. Results and Discussion: All animals survived after surgery with no aneurysm formation or thrombus observed. Endothelialization of the PGS/PCL patch was observed on the endocardial surface, and cell infiltration into outer PCL layer occurred at 4 weeks, increasing with time. PGS zone had been replaced by a band of the alpha-smooth muscle cell actin-positive cells starting at 4 weeks. Both cardiac troponin l/actinin-positive cells and c-kit/GATA/CD45-positive cells were also observed. Elastin fibers deposition along the endocardial surface was observed at 4 weeks, which ultimately formed the organized elastin fibers at 16 weeks (Fig1). A large amount of organized elastin fibers deposited along the endocardial surfaces may contribute to the improvement of cardiac function. Echocardiography demonstrated the contractility of heart in PGS/PCL group improved at 16 weeks. In contrast, the ePTFE patch exhibited less cell infiltration, and no cardiac troponin Ⅰ/actinin-positive cells and elastic fiber deposition at 16 weeks. Figure 1. Elastin fibers deposition distributed along the endocardial surface after 16 weeks post implantation of PGS/PCL patch. Conclusions: The PGS/PCL patch was associated with much better functional and histological outcomes compared to the ePTFE control, and it demonstrated suitable biocompatibility and remodeling properties. Future work will investigate the growth potential and contractile properties of the PGS/PCL patch which could ultimately be used as a right ventricular outflow construction for pediatric patients.