Injectable hydrogel with dual-sensitive behavior for targeted delivery of oncostatin M to improve cardiac restoration after myocardial infarction.

Myocardial infarction (MI) is a common cardiovascular disease that seriously endangers human health and complex pathophysiology (, coronary artery obstruction, myocardial apoptosis, necrosis, inflammation, fibrosis, ) is involved. Therein, the loss of cardiomyocytes after MI in adults leads to gradual heart failure, which probably brings irreparable damage to the patient. Unfortunately, due to a cluster of limitations, currently used MI repair approaches always exhibit simple functions, low efficiency, and can hardly match the myocardial ischemia environment and clinical needs. In this study, we selected oncostatin M (OSM), a pleiotropic cytokine belonging to the interleukin-6 family that possesses an important role in cardiomyocyte dedifferentiation, cell proliferation, and regulation of inflammatory processes. Moreover, an injectable hydrogel with pH- and temperature-responsive behavior that can react with the acidic microenvironment of the ischemic myocardium was developed to deliver OSM locally. The functional hydrogel (poly (chitosan--citric acid--isopropyl acrylamide), P(CS-CA-NIPAM)) was fabricated by the facile reversible addition-fragmentation chain transfer polymerization and can be injected into the lesion site directly. After the gelation , the OSM-loaded hydrogel exhibited continuous and localized release of OSM in response to specific pH and changes in MI rats, thereby accelerating angiogenesis and proliferation of cardiomyocytes, inhibiting myocardial fibrosis and improving cardiac function effectively. This study may provide a new perspective for the application of dual-sensitive hydrogels clinically, especially in tissue engineering for MI repair and drug delivery.