RESUMO
Myocardial infarction (MI) is considered as a significant cause of death globally. Exosomes (EXOs) are essential for intercellular communication and pathophysiology of several cardiovascular diseases. Nevertheless, the short half-life and rapid clearance of EXOs leads to a lack of therapeutic doses delivered to the lesioned area. Therefore, an injectable silk fibroin and alginate (SF/Alg) composite hydrogel was developed to bind folate receptor-targeted EXOs (FA-EXOs) derived from H9C2 cells for the therapy of myocardial injury following myocardial infarction-ischemia/reperfusion (MI-I/R). The resulting composite exhibits a variety of properties, including adjustable gelation kinetics, shear-thinning injectability, soft and dynamic stability that adapts to the heartbeat, and outstanding cytocompatibility. After injected into the damaged rat heart, administration of SF/Alg + FA-EXOs significantly enhanced cardiac function as demonstrated by improved ejection fraction, fractional shortening and decreased fibrosis area. The results of real-time PCR and immunofluorescence staining show a remarkable up-regulation in the expression of proteins (CD31) and genes (VWF and Serca2a) related to the heart. Conversely, expression of fibrosis-related genes (TGF-ß1) decreased significantly. Therefore, the obtained SF/Alg + FA-EXOs system remarkably enhanced the intercellular interactions, promoted cell proliferation and angiogenesis, and achieved an outstanding therapeutic effect on MI.
Assuntos
Alginatos , Exossomos , Fibroínas , Hidrogéis , Infarto do Miocárdio , Alginatos/química , Animais , Infarto do Miocárdio/terapia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Fibroínas/química , Hidrogéis/química , Exossomos/metabolismo , Exossomos/química , Ratos , Ratos Sprague-Dawley , Linhagem Celular , MasculinoRESUMO
Extracellular vesicles (EVs) have been recognized as one of the promising specific drugs for myocardial infarction (MI) prognosis. Nevertheless, low intramyocardial retention of EVs remains a major impediment to their clinical application. In this study, we developed a silk fibroin/hydroxypropyl cellulose (SF/HPC) composite hydrogel combined with AC16 cell-derived EVs targeted modification by folic acid for the treatment of acute myocardial infarction repair. EVs were functionalized by distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) via noncovalent interaction for targeting and accelerating myocardial infarction repair.In vitro, cytocompatibility analyses revealed that the as-prepared hydrogels had excellent cell viability by MTT assay and the functionalized EVs had higher cell migration by scratch assay.In vivo, the composite hydrogels can promote myocardial tissue repair effects by delaying the process of myocardial fibrosis and promoting angiogenesis of infarct area in MI rat model.
Assuntos
Celulose , Celulose/análogos & derivados , Vesículas Extracelulares , Fibroínas , Hidrogéis , Infarto do Miocárdio , Infarto do Miocárdio/tratamento farmacológico , Animais , Vesículas Extracelulares/metabolismo , Fibroínas/química , Ratos , Celulose/química , Hidrogéis/química , Ratos Sprague-Dawley , Sobrevivência Celular/efeitos dos fármacos , Masculino , Polietilenoglicóis/química , Movimento Celular/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Ácido Fólico/química , Humanos , Linhagem CelularRESUMO
Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a higher prevalence among young individuals. Traditional oral or subcutaneous injections are often used to treat AGA, however, they may cause severe side-effects and therefore effective treatments for AGA are currently lacking. In this work, to treat AGA, we developed a composite paste system based on minoxidil (MXD)-loaded nanoparticles and valproic acid (VPA) with the assistance of roller-microneedles (roller-MNs). The matrix of composite paste systems is carboxymethyl cellulose (CMC), hyaluronic acid (HA) and polyvinylpyrrolidone (PVP). The roller-MNs can create microchannels in the skin to enhance drug transdermal efficiency. With the combined effects of the stimulation hair follicle (HF) regrowth by upregulating Wnt/beta-catenin of VPA and the mechanical microchannels induced by roller-MNs, the as-prepared composite paste systems successfully boost perifollicular vascularization, and activate hair follicle stem cells, thereby inducing notably faster hair regeneration at a lower administration frequency on AGA mouse model compared with minoxidil. This approach offers several benefits, including the avoidance of efficacy loss due to the liver's first-pass effect associated with oral drug, reduction in the risk of infection from subcutaneous injection, and significant decrease in the side effects of lower-dose MXD.