Three-Layered Hydrogel Microfiber Encapsulating Fiber-Shaped Hipsc-Derived Cardiac Tissue for Maturation Triggered by Electrical Stimulation

We propose a three-layered hydrogel microfiber for improving the stability of the encapsulated three-dimensional (3D) hiPSC-derived cardiac tissue. This three-layered microfiber consists of an outer calcium alginate hydrogel layer, an intermediate collagen hydrogel layer, and a core cardiac tissue layer. In addition to the conventional two-layered hydrogel microfiber with a calcium alginate hydrogel as an outer layer and a cardiac tissue as a core, our three-layered microfiber introduces an intermediate collagen hydrogel layer. This newly added intermediate layer serves as a scaffold for cardiomyocytes and improves tissue stability. While the conventional two-layered microfiber only preserved its tissue length in 18% of the total microfiber length, our three-layered fiber enabled to preserve its tissue length in 58% of the total microfiber length. Furthermore, electrical stimulation (5 V, 2 Hz, 2 ms) increased the sarcomere length, an indicator of myocardial maturity, of the cardiac tissue in the proposed three-layered fiber by 11% compared to that without electrical stimulation. This three-layered fiber could contribute to the development of a highly matured in vitro cardiac model for elucidation of pathology, drug efficacy evaluation, and transplantation.