Electrospun Fibrous PVDF-TrFe Scaffolds for Cardiac Tissue Engineering, Differentiation, and Maturation

Cardiac tissue engineering aims to create cardiac tissue constructs that recapitulate the structure and function of the native heart. This approach has been widely used for creating myocardial implants for regenerative medicine, and more recently, for developing in vitro cardiotoxicity screening assays. However, once the engineered myocardial tissues are implanted or subjected to pharmacological stimuli, their performance should be monitored. Currently, there is no biomaterial that promotes functional tissues assembly while providing real-time information about their function, in situ. In this study, the piezoelectric phenomenon is sought to be exploited, to measure the contractions generated by engineered cardiac tissues. A poly-(vinylidene fluoride) (PVDF)-based electrospun fiber scaffold is developed, and it is hypothesized that the contractions of cardiomyocytes in the scaffold will induce mechanical deformations, which will result in measurable electric voltage. The PVDF scaffolds are characterized and optimized for supporting formation of aligned, functional, cardiac tissues. The scaffolds' function is then validated as sensors for tissue contraction and it is demonstrated that they can sense contractions of tissues constructed from as few as 5 × 10⁵ cardiomyocytes. Furthermore, it is demonstrated that human induced pluripotent stem cells can be directly seeded and differentiated to cardiomyocytes, and then mature over the course of 40 days on the PVDF fiber scaffolds.