ROS scavenging activity of polydopamine nanoparticle-loaded supramolecular gelatin-based hydrogel promoted cardiomyocyte proliferation

Reactive oxygen species (ROS) play essential roles in cellular functions, but maintaining ROS balance is crucial for effective therapeutic interventions, especially during cell therapy. In this study, we synthesized an injectable gelatin-based hydrogel, in which polydopamine nanoparticles were entrapped using supramolecular interactions. The surfaces of the nanoparticles were modified using adamantane, enabling their interactions with β-cyclodextrin-conjugated with gelatin. We evaluated the cytotoxicity and antioxidant properties of the hydrogel on neonatal rat cardiomyocytes (NRCM), where it demonstrated the ability to increase the metabolic activity of NRCMs exposed to hydrogen peroxide (H2O2) after 5 days. Hydrogel-entrapped nanoparticle exhibited a high scavenging capability against hydroxyl radical, 1'-diphenyl-2-picrylhydrazyl radicals, and H2O2, surpassing the effectiveness of ascorbic acid solution. Notably, the presence of polydopamine nanoparticles within the hydrogel promoted the proliferation activity of NRCMs, even in the absence of excessive ROS due to H2O2 treatment. Additionally, when the hydrogel with nanoparticles was injected into an air pouch model, it reduced inflammation and infiltration of immune cells. Notably, the levels of anti-inflammatory factors, IL-10 and IL-4, were significantly increased, while the pro-inflammatory factor TNF-α was suppressed. Therefore, this novel ROS-scavenging hydrogel holds promise for both efficient cell delivery into inflamed tissue and promoting tissue repair.