Tissue engineered heart valves (TEHV) could be useful in the repair of congenital or acquired valvular diseases due to their potential for growth and remodeling. The development of biomimetic scaffolds is a major challenge in heart valve tissue engineering. One of the most important structural characteristics of mature heart valve leaflets is their intrinsic anisotropy, which is derived from the microstructure of aligned collagen fibers in the extracellular matrix (ECM). In the present study, we used a directional electrospinning technique to fabricate fibrous poly-(glycerol sebacate):poly(caprolactone) (PGS:PCL) scaffolds containing aligned fibers, which resembled native heart valve leaflet ECM networks. In addition, the anisotropic mechanical characteristics of fabricated scaffolds were tuned by changing the ratio of PGS:PCL to mimic the native heart valve’s mechanical properties. Primary human valvular interstitial cells (VICs) attached and aligned along the anisotropic axes of all PGS:PCL scaffolds with various mechanical properties. The cells were also biochemically active in producing heart valve-associated collagen, vimentin, and smooth muscle actin as determined by gene expression. The fibrous PGS:PCL scaffolds seeded with human VICs mimicked the structure and mechanical properties of native valve leaflet tissues and would potentially be suitable for the replacement of heart valves in diverse patient populations.

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Biomimetic materials with biomechanical properties resembling those of native tissues while providing an environment for cell growth and tissue formation, are vital for tissue engineering (TE). Mechanical anisotropy is an important property of native cardiovascular tissues and directly influences tissue function. This study reports fabrication of anisotropic cell‐seeded constructs while retaining control over the construct's architecture and distribution of cells. Newly synthesized poly‐4‐hydroxybutyrate (P4HB) is fabricated with a dry spinning technique to create anelastomeric fibrous scaffold that allows control of fiber diameter, porosity, and rate ofdegradation. To allow cell and tissue ingrowth, hybrid scaffolds with mesenchymalstem cells (MSCs) encapsulated in a photocrosslinkable hydrogel were developed. Culturing the cellularized scaffolds in a cyclic stretch/flexure bioreactor resulted in tissue formation and confirmed the scaffold's performance under mechanical stimulation. In vivo experiments showed that the hybrid scaffold is capable of withstanding physiological pressures when implanted as a patch in the pulmonary artery. Aligned tissue formation occurred on the scaffold luminal surface without macroscopic thrombus formation. This combination of a novel, anisotropic fibrous scaffold and a tunable native‐like hydrogel for cellular encapsulation promoted formation of 3D tissue and provides a biologically functional composite scaffold for soft‐tissue engineering applications.

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