Melt-electrowriting fibrous scaffolds modified with nano-topography structures promoting cardiomyocytes synergistic contraction.

Melt-electrowriting (MEW) is an emerging strategy to fabricate microfibrous scaffolds that mimic the functional collagen fibers present in the native extracellular matrix (ECM). However, the main challenge remains in producing the nanoscale features that are widely found in ECM. In this work, MEW polycaprolactone (PCL) fibrous scaffolds with nano-topography structures (NS) were prepared to promote cell growth. Parallel PCL fibers were coated with NS by self-induced crystallization, which enhanced the adhesion and spreading of H9C2 cells. Compared with pristine scaffolds, the NS scaffolds exhibited improved hydrophilicity with a lower water contact angle of ∼50.70°. NS scaffolds exhibited abundant nano sites, which are beneficial for the cell-scaffold interaction and for achieving living constructs at a high cell density. Furthermore, NS scaffolds promoted cell-cell interactions and synergistic contraction of neonatal mouse cardiomyocytes (CMs). Dendritic pseudopods enabled CMs to spread along preferentially parallel to the direction of the lamellar. RNA sequencing analyses further revealed that the NS scaffolds upregulate cell cycle regulation-related pathways, cell communication-related pathways, calcium regulation-related pathways, cell motility-related pathways, and cellular adhesion and spreading-related pathways. It is envisioned that the proposed NS scaffolds may serve as promising candidates for tissue regeneration and biomedical engineering applications.