Scaffold-free 3D printing for fabrication of biomimetic branched multinucleated cardiac tissue construct: A promising ex vivo model for in situ detection of drug-induced sodium ion channel responses

3D bioprinted cardiac constructs have the potential to develop into functional native tissue. Although bioengineered cardiac constructs can be a promising tool for evaluating cardiac responses, the intrinsic limitation in reproducing the well-defined structural and functional properties of native cardiac tissue within the generated substitute restricts their applications. Herein, for the first time, we have introduced a sophisticated scaffold-free de novo three-dimensional (3D) printing model (SFP) to regenerate biomimetic cardiac tissue with a multinucleated branched cellular structure similar to native tissue–like phenotypes. Furthermore, the formation of tight intracellular junctions expressing connexin 43 certifies the maturation of the fabricated structure. In addition, in situ measurement of the bioengineered cardiac construct`s physiologic sodium ion channel responses to known cardiac drugs was successfully performed. Hence, the proposed methodology recapitulates a significant milestone in developing biomimetic cardiac tissue structure and functionality in vitro and could be applied for regenerative therapies, disease modeling, and drug screening.