Abstract

Background: Poor grafted rate of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) via direct injection into the myocardium limits the efficacy of cardiac repair after myocardial infarction (MI). Chitosan-based scaffolds has regarded as functional biomaterial for designing delivery systems in cardiac therapies. This study aimed to enhancing the potency of cardiac repair with the hiPSC-CMs loaded chitosan cardiac patch (hCCMP). Methods: The patches were fabricated with chitosan. Characterization of the chitosan patches was evaluated through the detection of swelling rate and porosity. Biocompatibility of the hiPSC-CMs loaded patches was analysed by scanning electron microscope (SEM) and CCK8 assay. The mice were randomly divided into 4 groups (n=10 for each). Animals underwent MI-inductive surgery followed by epicardium implantation of hCCMP or Empty-patch (without hiPSC-CMs); Sham and MI mice without further intervention were set as control. 4 weeks after MI, heart function was measured via echocardiography. Engraftment was evaluated with human cardiac troponin T staining. Infarction size, left ventricular anterior wall thickness, cardiac remodeling, angiogenesis, arterialization and apoptosis was detected via immunofluorescence in infarcted boder area. Results: SEM showed that the chitosan patch had regular pore size and good 3D structure; porosity was about (96.7±0.37)%. On day3, the patch swelling rate was about (715±64.55)%. SEM, CCK8 assay showed a normal cells growth in the chitosan patch. The hiPSC-CMs grafted well with chitosan patch delivery systems and was associated with significantly improvement in LV heart function, infarction size, LV anterior wall thickness, cardiac remodeling, angiogenesis and cardiomyocyte apoptosis 4 weeks after MI. Conclusions: The 3D chitosan cardiac patch with hiPSC-CMs loaded can enhance the potency of cardiac repair after MI and present a novel and promising therapic strategy.

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