Engineering Bioinspired Antioxidant Materials Promoting Cardiomyocyte Functionality and Maturation for Tissue Engineering Application

Oxidative stress plays an important role in various pathological conditions, such as wound healing, inflammation, myocardial infarction, and biocompatibility of the materials. Antioxidant polymers to attenuate oxidative stress is an emerging field of biomaterial research with a huge impact in the field of tissue engineering and regenerative medicine. We describe here the fabrication and evaluation of an elastomeric antioxidant polyurethane (PUAO) for tissue engineering applications. Uniaxial and cyclic tensile testing, thermal analysis, degradation, cytotoxicity and antioxidant analysis was carried out. An in vitro oxidative stress model demonstrated that PUAO reduced intracellular oxidative stress in H9C2 cardiomyocytes (p < 0.05) and attenuated reactive oxygen species (ROS) induced cell death (p < 0.001). Under simulated ischemic reperfusion, PUAO could rescue hypoxia induced cell death. Further as a proof of concept, neonatal rat cardiomyocytes cultured on PUAO film displayed synchronous beating with mature phenotype showing expression of cardiac specific a-actinin, troponin-T, and connexin-43 proteins. Intracellular calcium transients established the functionality of cultured cardiomyocytes on PUAO film. Our study demonstrated the potential of this biomaterial to be developed into tissue engineered scaffold to attenuate oxidative stress for treatment of diseased conditions with increased oxidative stress, such as cardiovascular diseases, chronic wound healing, and myocardial infarction.