Injectable self-oxygenating cardio-protective and tissue adhesive silk-based hydrogel for alleviating ischemia after MI injury

Myocardial infarction (MI) is a major cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and non-contractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency to be used in regenerative medicine remains challenging. Here, we present a combinatorial strategy for cardiac repair, through the development of cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area. We achieve a sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels. We observe enhanced endothelialization under normoxia and anoxia. Furthermore, there is a marked improvement in vascularization that leads to an increment in the cardiomyocyte survival by approximately 30%, and reduction of the fibrotic scar formation in an MI animal rodent model. We also observe improved left ventricular systolic and diastolic functions by ~ 10 and 20%, respectively, with a ~25% higher ejection fraction at day 7. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.