Abstract Body (Do not enter title and authors here): Background: The low grafting rate of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) following direct injection into the myocardium limits the efficacy of cardiac repair after myocardial infarction (MI). Chitosan-based scaffolds have emerged as functional biomaterials for designing delivery systems in cardiac therapies. This study aimed to enhance the potency of cardiac repair using a hiPSC-CMs loaded chitosan cardiac muscle patch (hCCMP).
Methods: The patches were fabricated using chitosan. Characterization of the chitosan patches involved assessing their swelling rate and porosity. The biocompatibility of the hCCMP was analyzed through scanning electron microscopy (SEM) and the CCK8 assay. 16 Yorkshire swine (15-20 kg, 45-50 days of age) were randomly divided into 4 groups (n=4 per group): Sham, MI without further intervention, MI with an empty patch (without hiPSC-CMs), and MI with hCCMP implantation. One and four weeks post-MI, heart function, Infarction size, myocardial perfusion and metabolism were evaluated via cardiac PET-MRI. Engraftment was assessed through human cardiac troponin T staining. Histological analysis including left ventricular anterior wall thickness, cardiac remodeling, angiogenesis, arterialization, and apoptosis in the infarct border area were analyzed using immunofluorescence.
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 function, infarction size, angiogenesis and cardiomyocyte apoptosis in pigs 4 weeks after MI.
Conclusions: The 3D chitosan cardiac patch with hiPSC-CMs loaded can enhance the potency of cardiac repair in pigs after MI and present a novel and promising therapic strategy.