Combinatorial effects of surface plasma-treating and aligning PCL/chitosan nanofibers on the behavior of stem cell-derived cardiomyocytes for cardiac tissue engineering

Pluripotent stem cell (PSC)-derived cardiomyocytes offer vast potential in heart failure therapy, yet their immaturity poses challenges. To solve this issue, a multifaceted approach combining exclusive biochemical/ topographical cues in the design of substrates mimicking the cardiac extracellular matrix was followed. Firstly, polycaprolactone (PCL)/chitosan nanofibers were electrospun in a random and aligned fashion, thus forming myocardium-like constructs. The scaffolds were then subjected to Ar and N2 dielectric barrier discharge treatments, thus further improving their surface properties. The Ar plasma incorporated oxygen-containing functionalities onto the nanofibers surface with an additional implantation of nitrogen-containing groups upon N2 plasma treatment, which both enhanced fibers' wettability. No topographical/dimensional damages were detected post-plasma treatments, except for a slight decrease in the surface roughness of the aligned nanofibers, which led to a decrease in their tensile stress. Both plasmas significantly enhanced the adhesion of PSC-derived cardiomyocytes that displayed more circular versus highly elongated body/nucleus morphologies on random versus aligned nanofibers, respectively. Interestingly, the cell alignment was less pronounced on GeltrexTMcoated nanofibers. Furthermore, increased sarcomere distance and organization were observed on aligned plasma-treated nanofibers, suggesting an enhanced cell maturation. Overall, PCL/chitosan nanofibers with aligned orientation and plasma-induced surface chemistry hold promise in cardiac tissue engineering applications.