Abstract

The aim of the present work was the development of heart patches based on gelatin (G) and chondroitin sulfate (CS) to be used as implants to improve heart recovery after corrective surgery for critical congenital heart defects (CHD). Patches were prepared by means of electrospinning to obtain nanofibrous scaffolds and they were loaded with platelet lysate (PL) as a source of growth factors to further enhance the repair process. Scaffolds were characterized for morphology and mechanical properties and for the capability to support in vitro adhesion and proliferation of dermal fibroblasts in order to assess the system’s general biocompatibility. Adhesion and proliferation of endothelial cells and cardiac cells (cardiomyocytes and cardiac fibroblasts from rat fetuses) onto PL-loaded patches was evaluated. Patches presented good elasticity and high stiffness suitable for in vivo adaptation to heart contraction. CS improved adhesion and proliferation of dermal fibroblasts, as proof of their biocompatibility. Moreover, they enhanced the adhesion and proliferation of endothelial cells, a crucial mediator of cardiac repair. Cell adhesion and proliferation could be related to elastic properties, which could favor cell motility. The presence of platelet lysate and CS was crucial for the adhesion and proliferation of cardiac cells and, in particular, of cardiomyocytes: G/CS scaffold embedded with PL appeared to selectively promote proliferation in cardiomyocytes but not cardiac fibroblasts. In conclusion, G/CS scaffold seems to be a promising system to assist myocardial-repair processes in young patient, preserving cardiomyocyte viability and preventing cardiac fibroblast proliferation, likely reducing subsequent uncontrolled collagen deposition by fibroblasts following repair.

Highlights

  • About 1 in every 4 babies born with a heart defect has a critical congenital heart defect

  • Patches were prepared by means of electrospinning to obtain nanofibrous scaffolds and they were loaded with platelet lysate (PL) as a source of growth factors to further enhance the repair process

  • Optimal viscosity of gelatin solutions to obtain reproducible fibers was characterized in the range of 200–1500 mPa·s at 25 ◦ C [24]

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Summary

Introduction

About 1 in every 4 babies born with a heart defect has a critical congenital heart defect (critical CHD, known as critical congenital heart disease). These are often due to a failure of morphogenesis [1,2] The definitive therapeutic option for critical CHD, such as HLHS (hypoplastic left-heart syndrome) or ToF (tetralogy of Fallot), is a series of corrective surgeries in the first few years of Polymers 2018, 10, 208; doi:10.3390/polym10020208 www.mdpi.com/journal/polymers. These are generally palliative in nature, aimed at maintaining cardiac function as long as possible to increase the likelihood of heart transplant. These patches induce an inflammatory foreign-body response, resulting in their encasement in a stiff, fibrous, scar-like tissue without normal cardiac functionality [3,5,6]

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