Small Extracellular Vesicle Loaded 3D Bioprinted Cardiac Patch for Tissue Repair Post Myocardial Infarction
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Rajurkar, Pranshu Parimal
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Abstract
Myocardial infarction is a leading cause of morbidity worldwide, often leading to heart failure and death caused by severe damage to the cardiac tissue. While stem cells therapies have been explored to regenerate the injured tissue, they suffer from tumorigenicity, immune rejection, low engraftment rates and poor translation overall. Recently, small extracellular vesicles (sEVs), the mediators of paracrine signaling for stem cells, have emerged as cell-free therapies and have been shown to possess cardioprotective and regenerative potential. However, sEV therapies suffer from poor tissue targeting and fast clearance from the circulation when injected intravenously or locally. To overcome these shortcomings, the goal of this study was to fabricate a sEV loaded 3D bioprinted cardiac patch. We hypothesized that once implanted on the injured heart tissue, the patch will be able to control the release of the encapsulated sEVs and retain them on-site for better regenerative outcomes. We isolated sEVs from cardiac progenitor cells (CPC) and successfully fabricated a 3D bioprinted cardiac patch which sustained the release of the encapsulated sEVs for over two weeks. We showed that the CPC sEVs had a strong angiogenic, pro-proliferative and pro-migratory effect on endothelial cells and this functionality was retained by the sEV loaded patch in vitro. Taken together, this study demonstrates the potential of 3D bioprinted sEVs for cardiac tissue regeneration and sets a strong foundation for in vivo studies in the future.
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2024-04-29
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