An injectable ECM-like hydrogel with bioactive peptides and RepSox nanoparticles for myocardial infarction treatment

Injectable hydrogels have emerged as a promising strategy for the treatment of myocardial infarction (MI) by delivering therapeutic cargo factors to modulate the infarct microenvironment at different stages of progression. To address the loss of extracellular matrix in the early stage of MI and the negative remodeling of the ventricle caused by the activation of myocardial fibroblasts in the late stage of MI, an ECM (extracellular matrix)-Like composite hydrogel system was developed. The composite hyaluronic acid (HA) hydrogel system comprises the bioactive peptides (CGEKGPAGERG) and Repsox-loaded poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PEG-PLGA) nanoparticles (Repsox NPs). The incorporation of the bioactive peptides provides a stable and efficient system for promoting cell proliferation and migration, while the inclusion of RepSox NPs inhibits myocardial fibrosis and improves heart function in the long run. This composite hydrogel can be injected directly into infarcted hearts through minimally invasive administration after MI to promote angiogenesis, and it also modulates the function of cardiac fibroblasts to prevent undesirable heart remodeling at subsequent stages. Overall, this composite hydrogel system holds significant potential as a therapeutic strategy for the treatment of myocardial infarction.