Fabrication of scaffold-free tubular cardiac constructs using a Bio-3D printer

Abstract

A major challenge in cardiac tissue engineering is the host’s immune response to artificial materials. To overcome this problem, we established a scaffold-free system for assembling cell constructs using an automated Bio-3D printer. This printer has previously been used to fabricate other three-dimensional (3D) constructs, including liver, blood vessels, and cartilage. In the present study, we tested the function in vivo of scaffold-free cardiac tubular construct fabricated using this system. Cardiomyocytes derived from induced pluripotent stem cells (iCells), endothelial cells, and fibroblasts were combined to make the spheroids. Subsequently, tubular cardiac constructs were fabricated by Bio-3D printer placing the spheroids on a needle array. Notably, the spheroid fusion and beat rate in the constructs were observed while still on the needle array. After removal from the needle array, electrical stimulation was used to test responsiveness of the constructs. An increased beat rate was observed during stimulation. Importantly, the constructs returned to their initial beat rate after stimulation was stopped. In addition, histological analysis shows cellular reorganization occurring in the cardiac constructs, which may mimic that observed during organ transplantation. Taken together, our results indicate that these engineered cardiac tubular constructs, which address both the limited supply of donor tissues as well as the immune-induced transplant rejection, has potential to be used for both clinical and drug testing applications. To our knowledge, this is the first time that cardiac tubular constructs have been produced using optimized Bio-3D printing technique and subsequently tested for their use as cardiac pumps.