An Injectable Silk Sericin Hydrogel Promotes Cardiac Functional Recovery After Ischemic Myocardial Infarction

Objective: To study the injectable sericin hydrogel therapeutic effects in mouse MI model.Methods: We prepared an injectable in situ forming sericin hydrogel and investigated the therapeutic potential of sericin hydrogel in an acute myocardial infarction model in C57/BL6 mouse.After induced anterior MI,mice received intramyocardial injection of hydrogel directly into the infarct area.Echocardiograms were performed at 5d and 6w to evaluate cardiac function.To dissect the mechanism for the repair effects of sericin,we performed comprehensive in vitro analyses to investigate the response of cells in inflammation,apoptosis and vascularzation after incubation with sericin.Results: The injection of this sericin hydrogel into MI area reduces scar formation and infarct size,increases wall thickness and neovascularization,and inhibits the MIinduced inflammatory responses and apoptosis,thereby leading to a significant functional improvement.The potential therapeutical mechanisms have been further analyzed in vitro.Our results indicate that sericin downregulates pro-inflammatory cytokines(TNF-a and IL-18)and chemokine(CCL2)and reduces TNF-a expression by suppressing the TLR4-MAPK/NF-κB pathways.Moreover,sericin exhibits angiogenic activity by promoting migration and tubular formation of human umbilical vessel endothelial cells(HUVECs).Also,sericin stimulates VEGFa expression via activating ERK phosphorylation.Further,sericin protects endothelial cells and cardiomyocytes from apoptosis by inhibiting the activation of caspase 3.Together,these diverse biochemical activities of sericin protein lead to a significant recovery of cardiac function.Conclusion: we identify sericin,a natural protein,as a biomaterial suitable for myocardial repair and demonstrate that the in vivo application of this injectable sericin hydrogel can be an effective strategy for treating MI.