Pro-regenerative anisotropic nanofiber heart valve scaffold by inducing directional cell growth

Strategically integrating degradable polymer and bioactive polymer nanofiber yarn scaffolds establishes an innovative approach for fabricating anisotropic hydrogel scaffolds, which effectively induce cell directional growth and promote the deposition and remodeling of extracellular matrix in tissue-engineered heart valves (TEHV). Here, a series of anisotropic nanofiber-based biomimetic heart valve scaffolds were fabricated via electrospinning coupled with thermal stretching of polylactic acid and methacryloyl-modified gelatin (GelMA). High-speed directional traction and thermal stretching rearrangement during the forming process of scaffolds endow the scaffold with a high fiber orientation degree of 0.8, enhancing elastic modulus and elongation at break along the fiber orientation direction. Interestingly, cell spreading efficiency of the scaffold was significantly improved to 62 ± 4.3 % from GelMA hydrogel group of 8.6 ± 5.5 %, simulating the mechanical and biological traits of native valve tissues. Notably, high GelMA content (40 %) endows the scaffolds with super-hydrophilicity and bioactivity, supporting the cell adhesion, proliferation and chondrogenic differentiation. Moreover, the scaffolds with an orientation degree of 0.8 facilitate the orderly cell growth and dynamic remodeling of extracellular matrix, demonstrate low expression levels of osteogenic genes and minimal calcium deposition under osteogenic induction, exhibiting optimal potential for osteogenesis inhibition and anti-calcification. This work significantly enhances the potential of the fully aligned scaffold for TEHV, while realizing innovation in the customization of directionally scaffolds integrated by degradable and bioactive polymers.