| Myocardial infarction?MI?leads to the mass death of cardiomyocytes accompanying with the unfavorable alternation of microenvironment,a fibrosis scar deprived of electrical communications,and the lack of blood supply in the infarcted myocardium.The three factors are inextricably intertwined and result in a conservative MI therapy efficacy in clinic.A combination approach pertinently targeted to these three points would be favorable to rebuild the heart functions.Here,a conductive injectable hydrogel was constructed to load plasmid DNA encoding eNOs?endothelial nitric oxide synthase?nanocomplexes and adipose derived stem cells?ADSCs?for treating MI.The conductive hydrogels,ADSCs,and up-regulated eNOs expression would rebuild heart functions and promote myocardium regeneration.A multi-armed and conductive crosslinker tetraaniline-polyethylene glycol diacrylate?TA-PEG?was synthesized,which can react with thiolated hyaluronic acid?HA-SH?to in situ form a hydrogel with the soft and anti-fatigue mechanical property and conductive property(G=2.32×10-4 S/cm).After encapsulation lipofectamine 2000/plasmid DNA-eNOs nanocomplexes and ADSCs,TA-PEG/HA-SH/ADSCs/Gene hydrogel system was injected into the infarcted myocardium of SD rats.The increasing expression of eNOs in myocardial tissue was confirmed by qRT-PCR and the heightening of nitrite concentration,accompanying with upregulation of proangiogenic growth factors and myocardium related mRNA.By the results of electrocardiography,cardiogram,and histological analysis,a distinct increase of ejection fraction?EF?,shortened QRS interval,smaller infarction size,less fibrosis area,and higher vessel density were observed,indicating a significant improvement of heart functions.Administration of genes and ADSCs through a conductive injectable hydrogel,which was designed with the definite aim to target the symptoms of an infarcted myocardium,did benefit to promote the cardiac function and facilitate myocardium regeneration. |
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