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Abstract AimsWe have shown that human cardiac muscle patches (hCMPs) containing three different types of cardiac cells—cardiomyocytes (CMs), smooth muscle cells (SMCs), and endothelial cells (ECs), all of which were differentiated from human pluripotent stem cells (hPSCs)—significantly improved cardiac function, infarct size, and hypertrophy in a pig model of myocardial infarction (MI). However, hPSC-derived CMs (hPSC-CMs) are phenotypically immature, which may lead to arrhythmogenic concerns; thus, since hPSC-derived cardiac fibroblasts (hPSC-CFs) appear to enhance the maturity of hPSC-CMs, we compared hCMPs containing hPSC-CMs, -SMCs, -ECs, and -CFs (4TCC-hCMPs) with a second hCMP construct that lacked hPSC-CFs but was otherwise identical [hCMP containing hPSC-CMs, -AECs, and -SMCs (3TCC-hCMPs)]. Methods and resultshCMPs were generated in a fibrin scaffold. MI was induced in severe combined immunodeficiency (SCID) mice through permanent coronary artery (left anterior descending) ligation, followed by treatment with cardiac muscle patches. Animal groups included: MI heart treated with 3TCC-hCMP; with 4TCC-hCMP; MI heart treated with no patch (MI group) and sham group. Cardiac function was evaluated using echocardiography, and cell engraftment rate and infarct size were evaluated histologically at 4 weeks after patch transplantation. The results from experiments in cultured hCMPs demonstrate that the inclusion of cardiac fibroblast in 4TCC-hCMPs had (i) better organized sarcomeres; (ii) abundant structural, metabolic, and ion-channel markers of CM maturation; and (iii) greater conduction velocities (31 ± 3.23 cm/s, P < 0.005) and action-potential durations (APD50 = 365 ms ± 2.649, P < 0.0001; APD = 408 ms ± 2.757, P < 0.0001) than those (velocity and APD time) in 3TCC-hCMPs. Furthermore, 4TCC-hCMPs transplantation resulted in better cardiac function [ejection fraction (EF) = 49.18% ± 0.86, P < 0.05], reduced infarct size (22.72% ± 0.98, P < 0.05), and better engraftment (15.99% ± 1.56, P < 0.05) when compared with 3TCC-hCMPs (EF = 41.55 ± 0.92%, infarct size = 39.23 ± 4.28%, and engraftment = 8.56 ± 1.79%, respectively). ConclusionCollectively, these observations suggest that the inclusion of hPSC-CFs during hCMP manufacture promotes hPSC-CM maturation and increases the potency of implanted hCMPs for improving cardiac recovery in mice model of MI. 

Abstract Layered oxide cathode with a Li‐O‐vacancy configuration offers high capacity by leveraging additional oxygen redox reactions. However, it faces severe challenges of sluggish kinetics of oxygen redox reactions and lattice oxygen loss, resulting in slow Li⁺diffusion and rapid electrochemical degradation. Herein, Ti is introduced as electrochemical inactive element into Li‐O‐vacancy configuration to form Mn/vacancy/Ti arrangement within transition metal layers of layered oxide, achieving a marked increase in average output voltage at high current density compared with Ti‐free counterpart. Not only voltage hysteresis between charge and discharge processes can be significantly reduced, but rate capability can be heightened in Li_4/7[□_1/7Ti_1/7Mn_5/7]O₂by means of retrained over‐potential and improved Li⁺diffusivity. Furthermore, theoretical calculations suggest that these improvements stem from Ti substitution, which elongates the Li─O bond and lowers the Li⁺migration energy barrier. Besides, in situ differential electrochemical mass spectrometry and soft X‐ray absorption spectroscopy reveal the modified Li‐O‐vacancy configuration enables reversible anionic and cationic redox behaviors during cycling. These findings provide a promising strategy for tailoring oxygen redox activity and accelerating Li⁺diffusion kinetics in layered cathode materials with oxygen redox chemistry.