Enhanced Cardiac Differentiation of Human Cardiovascular Disease Patient-Specific Induced Pluripotent Stem Cells by Applying Unidirectional Electrical Pulses Using Aligned Electroactive Nanofibrous Scaffolds

Abstract

In the embryonic heart, electrical impulses propagate in a unidirectional manner from the sinus venosus and appear to be involved in cardiogenesis. In this work, aligned and random polyaniline/polyetersulfone (PANI/PES) nanofibrous scaffolds doped by Camphor-10-sulfonic acid (β) (CPSA) were fabricated via electrospinning and used to conduct electrical impulses in a unidirectional and multidirectional fashion, respectively. A bioreactor was subsequently engineered to apply electrical impulses to cells cultured on PANI/PES scaffolds. We established cardiovascular disease-specific induced pluripotent stem cells (CVD-iPSCs) from the fibroblasts of patients undergoing cardiothoracic surgeries. The CVD-iPSCs were seeded onto the scaffolds, cultured in cardiomyocyte-inducing factors, and exposed to electrical impulses for 1 h/day, over a 15-day time period in the bioreactor. The application of the unidirectional electrical stimulation to the cells significantly increased the number of cardiac Troponin T (cTnT+) cells in comparison to multidirectional electrical stimulation using random fibrous scaffolds. This was confirmed by real-time polymerase chain reaction for cardiac-related transcription factors (NKX2.5, GATA4, and NPPA) and a cardiac-specific structural gene (TNNT2). Here we report for the first time that applying electrical pulses in a unidirectional manner mimicking the unidirectional wave of electrical stimulation in the heart, could increase the derivation of cardiomyocytes from CVD-iPSCs.

Sequential application of mineralized electroconductive scaffold and electrical stimulation for efficient osteogenesis

“…46,47 Although the electrodes were not completely isolated from the medium, the presence of scaffolds on the electrodes interferes with physical contact between the electrodes and the medium. 46,47 Although the electrodes were not completely isolated from the medium, the presence of scaffolds on the electrodes interferes with physical contact between the electrodes and the medium.…”

“…To deliver electrical stimuli, the bioreactor described in the previous study 47 was used (Fig. To deliver electrical stimuli, the bioreactor described in the previous study 47 was used (Fig.…”

Electrospun electroactive nanofibers of gelatin‐oligoaniline/Poly (vinyl alcohol) templates for architecting of cardiac tissue with on‐demand drug release

“…Mohammadi et al synthesized polyaniline‐based nanofibers for cardiac tissue engineering. It was demonstrated that the conductive substrate enhance the induced pluripotent stem cell differentiation to myocardium cell in comparison with nonconductive substrate . Also, it has been reported that the agarose‐aniline pentamer enhances the neural regeneration .…”

Fabrication of graphene‐silver/polyurethane nanofibrous scaffolds for cardiac tissue engineering

“…Nanoscale gold structures are employed in cardiac scaffolds including nanowires, spheres, rods, or even films . On the other hand, electroactive polymers such as polypyrrole (PPy) and polyaniline (PANI) with controllable conductive properties known as smart materials are well studied in cardiac tissue engineering. By understanding the extraordinary properties of carbon‐based nanomaterials such as carbon nanotubes, carbon nanofibers, and graphene family, they are considered as acceptable candidates for incorporation into other nonconductive materials to obtain conducive scaffolds.…”