Oxygen releasing and antioxidant breathing cardiac patch delivering exosomes promotes heart repair after myocardial infarction

Constant oxygen supply is inevitable for cardiac tissue function and survival. Myocardial infarction (MI) leaves heart tissue in a state of oxygen deficiency, causing oxidative stress and irreversible death of cardiomyocytes. Although vital in treating MI, restoration of oxygen supply and attenuation of oxidative stress has not been successfully utilized as a therapeutic strategy. Herein, we developed and evaluated an oxygen releasing antioxidant nanofibrous bi-layered cardiac patch (PUAO-CPO-Collagen) supplemented with adipose derived stem cell exosomes (ADSC-EXO) to promote heart repair. Antioxidant polyurethane was synthesised and calcium peroxide (CPO) was incorporated as an oxygen releasing material. The bilayered cardiac patch consists of an oxygen releasing antioxidant polyurethane, electrospun over a porous collagen scaffold and supplemented with adipose derived stem cell exosomes. The patch demonstrated sustained release of oxygen and exosomes. Under in-vitro conditions, bilayered patch and ADSC exosomes illustrated proliferative, pro-angiogenic and pro-survival effect. In an in-vivo rat MI model, the bi-layered patch demonstrated enhanced cardiac function, reduced scar formation, significantly attenuating adverse cardiac remodelling through improved angiogenesis and decreased oxidative stress. Our study demonstrated an innovative and promising cell free biomaterial approach for delivering oxygen, promoting angiogenesis, and attenuating oxidative stress for enhanced heart regeneration after myocardial infarction.