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Myocardial infarction (MI) occurs due to the obstruction of coronary arteries, a major crux that restricts blood flow and thereby oxygen to the distal part of the myocardium, leading to loss of cardiomyocytes and eventually, if left untreated, leads to heart failure. MI, a potent cardiovascular disorder, requires intense therapeutic interventions a...
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... Currently, the approaches for preventing cardiac fibrosis after MI generally involve i) application of biomaterials (e.g., injectable hydrogels and cardiac patches), to support the infarcted tissue and reduce elevated wall stress, [10][11][12][13][14][15][16] and ii) delivery of antifibrotic drugs or bioactive factors to inhibit specific signaling pathways related to fibrosis (e.g., transforming growth factor-(TGF-)-related signaling pathways that play a dominant role in myocardial fibrosis by inducing the transformation of cardiac fibroblasts into myofibroblasts and promoting the production and deposition of collagens). [17][18][19][20][21] Recently, microRNAs (miRNAs), a class of small noncoding RNAs that play crucial roles in regulating gene expression, have been discovered to treat fibrosis. ...
Myocardial infarction (MI) is a cardiovascular disease that poses a serious threat to human health. Uncontrolled and excessive cardiac fibrosis after MI has been recognized as a primary contributor to mortality by heart failure. Thus, prevention of fibrosis or alleviation of fibrosis progression is important for cardiac repair. To this end, a biocompatible microneedle (MN) patch based on gelatin is fabricated to load exosomes containing microRNA‐29b (miR‐29b) mimics with antifibrotic activity to prevent excessive cardiac fibrosis after MI. Exosomes are isolated from human umbilical cord mesenchymal stem cells and loaded with miR‐29b mimics via electroporation, which can be internalized effectively in cardiac fibroblasts to upregulate the expression of miR‐29b and downregulate the expression of fibrosis‐related proteins. After being implanted in the infarcted heart of a mouse MI model, the MN patch can increase the retention of loaded exosomes in the infarcted myocardium, leading to alleviation of inflammation, reduction of the infarct size, inhibition of fibrosis, and improvement of cardiac function. This design explored the MN patch as a suitable platform to deliver exosomes containing antifibrotic biomolecules locally for the prevention of cardiac fibrosis, showing the potential for MI treatment in clinical applications.
... With current treatment methods for heart failure being invasive, expensive, and unfeasible for much of the globe, there has been extensive recent research on alternative treatment methods for heart failure. In particular, one area of research focus is on cardiac tissue engineering to either transplant myocardial cells into the area of infarct or otherwise facilitate the self-regeneration of the myocardium after an MI 264,265 . A promising candidate in the area of myocardial regenerative medicine is the use of biomaterial cell scaffolds, especially those made of extracellular matrix proteins, to encourage the growth and proliferation of cells. ...
Platelets play a major role in vivo in preventing bleeding, hemostasis, and contributing to uncontrolled clotting, thrombosis. Platelets are impacted in health and disease by the other cells they encounter in blood flow, including red blood cells (RBCs), white blood cells (WBCs), and the endothelial cell monolayer lining blood vessel walls. Despite this importance, the effect other cell types have on platelets in disease has yet to be fully explored, in part due to a lack of proper models to study human platelet behavior. In this thesis, we develop new, tunable in vitro methods to study platelet behavior that can be altered depending on disease conditions. We examined platelet adhesion to a confluent endothelial cell monolayer cultured on crosslinked extracellular matrix proteins, which were exposed via manual damage. We attached the damaged endothelial cells to a parallel plate flow chamber and monitored human platelet behavior and adhesion over a wide variety of blood flow conditions. This model was validated using a known anti-platelet compound and we identified two additional novel compounds that significantly reduced platelet adhesion when administered either to blood or to the endothelial cells themselves. Many diseases, including acute lung injury, venous and arterial thrombosis, and sepsis, fall under the umbrella of ‘thromboinflammation,’ when blood clots occur in combination with an overzealous immune cell response. A hallmark of these diseases is the presence of leukocyte-platelet aggregates at the site of inflammation. To capture this phenomenon, we included inflammation of endothelial cells in our flow model to facilitate the adhesion of leukocyte-platelet aggregates. We then utilized model polymeric drug carriers to reduce platelet adhesion to the inflamed endothelium by interfering with platelet-bound leukocytes. Specifically, platelet adhesion in this model decreased by approximately two-fold after 2 µm polystyrene particles were introduced into the system. We verified that this impact of particles is translatable in vivo using a mouse model of systemic inflammation; 2 µm particles significantly reduced platelet adhesion to the mouse mesentery by up to 62% in comparison to non-particle controls. These findings represent a potential new particle-based therapeutic to reduce platelet accumulation in thromboinflammatory diseases by diverting platelet-leukocyte aggregates away from areas of inflammation. Patients with sickle cell disease (SCD) have RBCs that are more stiff than non-SCD controls; we explored the impact that these stiff RBCs have on platelet behavior in blood flow in vitro using SCD patient whole blood samples and a model system where healthy RBCs are artificially stiffened to mimic SCD. The magnitude of SCD platelet adhesion varied greatly depending on patient treatment regimen, though untreated patients had the highest platelet adhesion in comparison to non-SCD controls. Our artificial system allowed us to examine the impact of stiff RBCs on platelet adhesion in a controlled environment, providing knowledge that can help inform how to provide chronic transfusions of RBCs to SCD patients to best reduce excessive platelet adhesion and clotting. We also determined that carbon monoxide releasing molecules (CORMs) reduce excessive platelet adhesion for a subset of patients, a promising new potential therapeutic for SCD. Overall, this work represents new methods to study platelet behavior under different disease conditions as well as novel potential therapeutics to modulate platelet adhesion in thromboinflammation and SCD.
... This section mainly considers the crosslinking of viscous liquids to form hydrogels as well as the deposition on hydrogels by plasma engineering (figure 3). Engineered hydrogels are a key material, e.g. for various biomedical applications [33,34]. In addition, plasma-induced polymerization of other suitable liquids and deposition on such liquids is touched on briefly. ...
Manmade soft materials are important in a wide range of technological applications and play a key role in the development of future technologies, mainly at the interface of synthetic and biological components. They include gels and hydrogels, elastomers, structural and packaging materials, micro and nanoparticles as well as biological materials. Soft materials can be distinguished from liquids owing to their defined shape and from hard materials by the deformability of their shape. This review article provides an overview of recent progress on the plasma engineering and processing of softer materials, especially in the area of synthesis, surface modification, etching, and deposition. The article aims to demonstrate the extensive range of plasma surface engineering as used to form, modify, and coat soft materials focusing on material properties and potential applications. In general, the plasma provides highly energetic, non-equilibrium conditions at material surfaces requiring to adjust the conditions for plasma-surface interaction to account for the specifics of soft matter, which holds independent of the used plasma source. Plasma-induced crosslinking and polymerization of liquids is discussed to transform them into gel-like materials as well as to modify the surface region of viscous liquids. A major field covers the plasma surface engineering of manmade soft materials with the help of gaseous reactive species yielding ablation, nanostructuring, functionalization, crosslinking, stiffening, and/or deposition to obtain demanded surface properties or adhesion to dissimilar materials. Finally, plasma engineering of rigid materials is considered to induce surface softening for the enhanced contact with tissues, to allow interaction in aqueous media, and to support bonding to soft matter. The potential and future perspectives of plasma engineering will be discussed in this review to contribute to a higher knowledge of plasma interaction with sensitive materials such as soft matter.
To reduce the mortality of myocardial infarction (MI), accurate detection of the infarct and appropriate prevention against ischemia/reperfusion (I/R) induced cardiac dysfunction are highly desired. Considering that vascular endothelial growth factor (VEGF) receptors are overexpressed in the infarcted heart and VEGF mimetic peptide QK binds specifically to VEGF receptors and activates vascularization, the PEG-QK-modified, gadolinium-doped carbon dots (GCD-PEG-QK) were formulated. This research aims to investigate the magnetic resonance imaging (MRI) capability of GCD-PEG-QK on myocardial infarct and their therapeutic effect on I/R-induced myocardial injury. These multifunctional nanoparticles exhibited good colloidal stability, excellent fluorescent and magnetic property, and satisfactory biocompatibility. Intravenous injection of GCD-PEG-QK nanoparticles post myocardial I/R displayed accurate MRI of the infarct, enhanced efficacy of QK peptide on pro-angiogenesis, and amelioration of cardiac fibrosis, remodeling and dysfunction, probably via the improvement on QK's in vivo stability and MI-targeting. Collectively, the data suggested that this theranostic nanomedicine can realize precise MRI and effective therapy for acute MI in a non-invasive manner.
Cardiac patch, a scaffold layered on the surface of the heart that can provide mechanical and regeneration support for damaged myocardium, has provided a promising solution to treat severe myocardial infarction (MI). In this work, a fibrin based cardiac patch loaded with neuregulin-1 (NRG-1) is developed to attach locally to the infract area of heart. The composite patch exhibited good biocompatibility and promoted cardiomyocyte proliferation in vitro via NRG-1/ErbB signaling. Moreover, implantation of this patch to the infracted border zone reduced cell apoptosis, promoted angiogenesis and inhibited fibrosis, which reduced infraction size and improved cardiac function consequently. Thus, the combination of natural biomaterial fibrin and bioactive factor NRG-1 might have a promising potential for clinical application of MI treatment.
