Oxygen-generating microparticles enhance viability and functionality of human pluripotent stem cell-derived cardiomyocytes

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a promising therapy for myocardial infarction (MI), but their survival is severely limited by the hypoxic infarct environment. The optimal oxygen levels required to maintain the viability and functionality of hiPSC-CMs remain poorly defined. This study aimed to develop a controlled oxygen-delivery system to support engineered heart tissue (EHT) for cardiac regeneration. Oxygen-generating particles (OGPs) were engineered using peroxide (sodium percarbonate) and antioxidant (β-carotene) components encapsulated in PLGA microparticles. The effects of OGPs on hiPSC-CMs were evaluated through oxidative stress assays, cell viability analysis, and contractility measurements. RNA-seq was performed to investigate gene expression changes in hiPSC-CMs in response to OGPs and hypoxic stress. Transcriptomic analysis revealed that genes associated with CM maturation and contractile function were upregulated following OGP pretreatment. RNA-seq further demonstrated activation of oxygen-responsive metabolic pathways that facilitated cellular adaptation to hypoxic stress. OGP-mediated oxygen delivery offers a promising strategy for oxidative preconditioning and significantly improves the regenerative efficacy of hiPSC-CM-based cardiac therapies.