Increased therapeutic factors and retention of IONP-NVs substantially enhance therapeutic potential for cardiac repair.

Tissue engineering has emerged as a promising approach to viable small-diameter vascular grafts that may be used to treat cardiovascular diseases. One challenge in constructing such blood vessels is proper localization of endothelial cells and smooth muscle cells, as well as promotion of their cellular functions to generate functional tissues. Thus far, construction of small-diameter vascular substitutes with both endothelial and muscular tissues, which is essential for the grafts to acquire antithrombosis function and sufficient strength to avoid thrombus formation as well as to withstand blood pressure, has not yet been demonstrated. In this study, we engineer small-diameter blood vessel grafts containing both functional endothelial and muscular cell layers, which has been demonstrated in vivo in a living rat model. Our construction of the blood vessel grafts uses vascular-tissue-derived extracellular matrix bioinks and a reservoir-assisted triple-coaxial cell printing technique. The prematured vessel was implanted for three weeks as a graft of rat abdominal aorta in a proof-of-concept study where all implants showed great patency, intact endothelium, remodeled smooth muscle, and integration with host tissues at the end of the study. These outcomes suggest that our approach to tissue-engineered biomimetic blood vessels provides a promising route for the construction of durable small-diameter vascular grafts that may be used in future treatments of cardiovascular diseases.

Priming human BM-MSCs with engineered HGF-MSCs in vivo significantly improves therapeutic potential for myocardial infarction.

Engineered human cardiac tissues have been utilized for various biomedical applications, including drug testing, disease modeling, and regenerative medicine. However, the applications of cardiac tissues derived from human pluripotent stem cells are often limited due to their immaturity and lack of functionality. Therefore, in this study, we establish a perfusable culture system based on in vivo-like heart microenvironments to improve human cardiac tissue fabrication. The integrated culture platform of a microfluidic chip and a three-dimensional heart extracellular matrix enhances human cardiac tissue development and their structural and functional maturation. These tissues are comprised of cardiovascular lineage cells, including cardiomyocytes and cardiac fibroblasts derived from human induced pluripotent stem cells, as well as vascular endothelial cells. The resultant macroscale human cardiac tissues exhibit improved efficacy in drug testing (small molecules with various levels of arrhythmia risk), disease modeling (Long QT Syndrome and cardiac fibrosis), and regenerative therapy (myocardial infarction treatment). Therefore, our culture system can serve as a highly effective tissue-engineering platform to provide human cardiac tissues for versatile biomedical applications.

Neutrophils are critical mediators of both the initiation and resolution of inflammation after myocardial infarction (MI). Overexuberant neutrophil signaling after MI exacerbates cardiomyocyte apoptosis and cardiac remodeling while neutrophil apoptosis at the injury site promotes macrophage polarization toward a pro-resolving phenotype. Here, we describe a nanoparticle that provides spatiotemporal control over neutrophil fate to both stymie MI pathogenesis and promote healing. Intravenous injection of roscovitine/catalase-loaded poly(lactic-co-glycolic acid) nanoparticles after MI leads to nanoparticle uptake by circulating neutrophils migrating to the infarcted heart. Activated neutrophils at the infarcted heart generate reactive oxygen species, triggering intracellular release of roscovitine, a cyclin-dependent kinase inhibitor, from the nanoparticles, thereby inducing neutrophil apoptosis. Timely apoptosis of activated neutrophils at the infarcted heart limits neutrophil-driven inflammation, promotes macrophage polarization toward a pro-resolving phenotype, and preserves heart function. Modulating neutrophil fate to tune both inflammatory and reparatory processes may be an effective strategy to treat MI.