Adaptive hydrogel platform for nitric oxide release and post-infarction cardiac microenvironment modulation

After myocardial infarction (MI), oxidative stress, inflammatory response and myocardial fibrosis severely impair tissue regeneration. Aiming at the problem that multifunctional hydrogel systems are difficult to achieve precise therapeutic regulation due to limited response characteristics and insufficient synergistic effect. Here, we developed an adaptive hydrogel platform for targeted nitric oxide (NO) release and post-infarction cardiac microenvironment modulation. A small molecule phenylboronic acid-based cross-linker (N(BA)4) with a four-arm topology was reported for the first time, and it was combined with Nitroso glutathione (GSNO)-modified polyvinyl alcohol (PVA) to prepare the hydrogel platform. For the multi-stage of myocardial repair, bioactive microspheres with programmed delivery function were prepared, which could rapidly release the salvianolic acid B in the pre-infarct stage to exert antioxidant and pro-angiogenic effects, and continuously release the fibrosis inhibitor Galunsertib in the post-infarct stage to inhibit fibrosis. The pathologically responsive composite hydrogel system enables precise and efficient MI therapy through a cascade-triggered drug release mechanism and multi-pathway synergy. It provides a novel and promising strategy to overcome the challenges of different pathological stages in the infarcted cardiac microenvironment.