Effects And Mechanisms Of 3D-Printed PGS-PCL Scaffolds On Cardiac Remodeling After Myocardial Infarction

Objective Myocardial infarction is the leading cause of death.Tissue engineered cardiac scaffolds provide mechanical support for the injured myocardium and facilitated tissue repair.The aims of the study are to fabricate a hybrid polymeric scaffold composed of poly(glycerol sebacate)(PGS)and poly(ε-caprolactone)(PCL)by 3D printing technology,implant the PGS-PCL scaffold epicardially in a rat model of acute myocardial infarction,and further elucidate the impact of PGS-PCL scaffold on cardiac function post-infarct and the detailed mechanism of improving myocardial remodeling.An additional aim is to further expand the potential application of annular-shaped 3D printed PGS-PCL scaffold as a cardiac restraint device.Methods PGS-PCL scaffolds were fabricated using fused deposition modelling 3D-printing technology,and PCL and PGS scaffolds were printed simultaneously as controls.Scanning electron microscopy was employed to investigate the structural features of the 3D printed scaffolds.Mechanical properties of different scaffolds were testified via mechanical tests.In vitro enzymatic degradation and cell viability assay were performed to examine biodegradability and biocompatibility of the 3D printed scaffolds,respectively.Subsequently,in vivo implantations of PGS-PCL,PGS and PCL scaffolds were performed in a rat model of acute myocardial infarction.Left ventricular contractile performance was evaluated through echocardiography 7 and 28 days post-implantation,respectively.Moreover,histological assessments were performed 28 days post-implantation: infarction size and left ventricular wall thickness were assessed using Masson’s trichrome staining;revascularization of border region and scaffold region was evaluated through immunofluorescence co-localization of blood vessel SMA and endothelial cells;infiltration of M1 and M2 macrophages into border region and scaffold region was assessed via immunofluorescence staining;TUNEL staining was performed to estimate myocardium apoptosis in the border region;expression level of p53 in the border region and was estimated using western blotting method.Furthermore,annular-shaped 3D printed PGS-PCL scaffolds were implanted in a rat model of subacute myocardial infarction.Echocardiography were performed 7 and 28 days post-implantation to assess cardiac functional changes.Histological evaluation was alsoperformed 28 days post-implantation via Masson’s trichrome staining.Results The 3D printed PGS-PCL scaffold possesses interconnected micropores and stacked construction with regular criss-crossed filaments.Compare with PCL and PGS scaffold,PGS-PCL scaffold exhibits favourable mechanical strength,elasticity,biodegradability and biocompatibility.When implanted onto the infarct myocardium,PGS-PCL scaffold could provide sufficient mechanical support for the injured tissue and improve myocardial remodeling: the PGS-PCL scaffold improved and preserved heart function post-implantation;on the morphological level,the scaffold reduced ventricular wall thinning and attenuated infarct size;on the cellular level,it enhanced vascular density,increased M2 macrophage infiltration,reduced myocardial apoptosis rate and inhibited expression level of p53.Furthermore,annular-shaped 3D printed PGS-PCL scaffolds improved cardiac pumping function and prevented left ventricular dilation.Conclusion 3D printed PGS-PCL scaffolds possess superior structural features,mechanical properties and biodegradability and biocompatibility.The PGS-PCL scaffolds significantly improved cardiac remodeling after myocardial infarction through providing sufficient mechanical support and stimulating tissue repair.Moreover,annular-shaped 3D printed PGS-PCL scaffolds could function as cardiac restraint device to prevent ventricular dilation post-infarct.