Student PUSAN NATIONAL UNIVERSITY SCHOOL OF MEDICINE, United States
Abstract: 3D bioprinting has been widely used for cardiac tissue engineering, offering precise control over cellular organization. Anisotropic alignment of cardiomyocytes is critical for mimicking native myocardium, as it enhances cytoskeletal elongation, sarcomere organization, and intercellular connectivity. While methods such as micropatterning and electrospun nanofibers have promoted alignment, the role of Au nanowires in directing anisotropic organization and their molecular effects remain unclear. This study aims to develop a 3D bioprinting strategy using gold (Au) nanowires to induce anisotropic alignment of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and enhance their structural organization, maturation, and intercellular communication. Aligned 3D bioprinting with Au nanowires improved cytoskeletal organization, increasing F-actin structures and sarcomere length. Aligned hESC-CMs exhibited upregulated maturation markers, including cTnI, MYH7, and MYL2, compared to randomly aligned CMs. Additionally, the expression of N-cadherin and connexin 43 increased, facilitating intercellular communication. Ang-1 and Ang-2, key regulators of cardiac contractility, were also upregulated. We found that Wnt signaling, particularly the noncanonical pathway, was activated in aligned hESC-CMs, influencing cytoskeletal remodeling and cell adhesion. Given the role of Wnt in connexin regulation, we propose that anisotropic bioprinting enhances intracellular communication through cell junction-mediated crosstalk. This study demonstrates that 3D bioprinting with Au nanowires is an effective strategy for engineering anisotropic cardiac tissues, with potential applications in regenerative medicine.
Funding Source: Supported by the National Research Foundation of Korea (NRF, RS-2023-00208466) and the Korean Fund for Regenerative Medicine (KFRM, RS-2022-00070441) from the Korea government, MSIT, and MOHW.
