Bioactive cardiac ECM hydrogel sequentially released VEGF and Ang-1 mimic peptides to promote the recovery of myocardial infarction

Vascular endothelial growth factor (VEGF) based therapeutic angiogenesis provided a promising treatment for myocardial infarction (MI). As a critical coordinated factor, angiopoietin-1 (Ang-1) and its mimic peptide (AMP) were revealed to promote VEGF-mediated vascular remodeling and maturation. In present study, a bioactive cardiac extracellular matrix (ECM) hydrogel was constructed which could realize the sequential release of VEGF and AMP in response to the upregulated Matrix Metalloproteinase-2 (MMP-2) in the ischemic microenvironment. This targeting delivery system could significantly enhance the formation of functional blood vessels, reduce cardiomyocytes apoptosis, and finally improve the cardiac function recovery in rats with MI. Therefore, the spatiotemporal sequential release system of VEGF and AMP was effective for vascular regeneration and tissue preservation, which provided a potent strategy for targeting therapy of MI.