Injectable myocardium-derived hydrogels with SDF-1α releasing for cardiac repair

Myocardial infarction (MI) is a predominant cause of morbidity and mortality globally. Therapeutic chemokines, such as stromal cell-derived factor 1α (SDF-1α), present a promising opportunity to treat the profibrotic remodeling post-MI if they can be delivered effectively to the injured tissue. However, direct injection of SDF-1α or physical entrapment in a hydrogel has shown limited efficacy. Here, we developed a sustained-release system consisting of SDF-1α loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) and an injectable porcine cardiac decellularized extracellular matrix (cdECM) hydrogel. This system demonstrated a sustained release of SDF-1α over four weeks while there is one week release for SDF-1α directly encapsulated in the cdECM hydrogel during in vitro testing. The incorporation of PLGA NPs into the cdECM hydrogel significantly enhanced its mechanical properties, increasing the Young's modulus from 561 ± 228 kPa to 1007 ± 2 kPa and the maximum compressive strength from 639 ± 42 kPa to 1014 ± 101 kPa. This nanocomposite hydrogel showed good cell compatibility after 7 days of culture with H9C2 cells, while the released SDF-1α retained its bioactivity, as evidenced by its chemotactic effects in vitro. Furthermore, in vivo studies further highlighted its significant ability to promote angiogenesis in the infarcted area and improve cardiac function after intramyocardial injection. These results demonstrated the therapeutic potential of combining local release of SDF-1α with the cdECM hydrogel for MI treatment.