Bioactive Peptide-Based Composite Hydrogel for Myocardial Infarction Treatment: ROS Scavenging and Angiogenesis Regulation.

After myocardial infarction (MI), the affected area of the myocardium falls into a state of ischemia and hypoxia, and subsequently, cardiomyocytes undergo a series of pathological changes and eventually transform into scar tissue. Therefore, restoring blood perfusion and reducing reactive oxygen species (ROS) are essential to promote the repair process of damaged myocardium. Here, the MMP12 (YWDAW) peptide which has a good antioxidant effect in deep-sea fish muscle, and the KRX (MRPYDANKR) peptide which shows a pro-angiogenesis effect from mammalian endothelial genes, were utilized collaboratively and loaded into an injectable GelMA hydrogel to achieve minimally invasive implantation and long-term retention at the MI site. The incorporation of bioactive peptides builds a stable and efficient system, which in addition to effectively removing ROS and promoting angiogenesis, avoids cell apoptosis and inflammation in the long run, and effectively inhibits the process of myocardial fibrosis. Both in vivo and in vitro experiments have shown that the combination of two short peptides with anti-oxidation and angiogenesis therapy can eventually achieve rapid repair of damaged myocardial tissue. This study fully demonstrated that natural functional peptides have great potential in promoting the repair and regeneration of infarcted hearts. STATEMENT OF SIGNIFICANCE: We have successfully synthesized antioxidant and pro-angiogenic peptides, which were subsequently incorporated into an injectable hydrogel matrix. This bioactive hydrogel system demonstrates dual therapeutic functions, effectively scavenging ROS while promoting angiogenesis, thereby facilitating cardiac tissue repair. Notably, the chemical synthesis approach employed in peptide production establishes a robust foundation for scalable manufacturing and broad biomedical applications, particularly in cardiovascular therapeutics.