Bioinspired trilayer poly(ε-caprolactone) scaffolds with native-like structures and mechanical property for heart valve constructs

Although valve replacement surgery is one of the primary treatments for patients with severe heart valve disease, current artificial valve options are lack of regenerative and remodeling potential, not suitable for pediatric and young patients. Inspired by the natural structures of heart valve leaflets, this study employed electrospinning technology to fabricate bioinspired trilayer poly(ε-caprolactone) scaffolds, aiming to replicate the microstructures and mechanical properties of native leaflets for tissue-engineered heart valves (TEHVs). Specifically, a collector with a honeycomb pattern was used to fabricate the middle layer, mimicking the spongiosa layer of native leaflets, while a roller collector was used to produce the orthogonal fiber alignment in the upper and lower layers. The prepared biomimetic tri-layered scaffold (BTS) not only mimicked the fiber alignment of native leaflets but also successfully reproduced the natural corrugation structure found in heart valve leaflets, generating a nonlinear stress-strain behavior resembling the “J-curve” observed in native leaflets. Furthermore, the anisotropic BTS exhibited elastic moduli (BTS-X: 12.50 ± 1.88 MPa; BTS-Y: 7.01 ± 1.12 MPa) and ultimate tensile strengths (UTS) (BTS-X: 8.09 ± 1.16 MPa; BTS-Y: 4.60 ± 0.75 MPa) in the orthogonal directions, close to those of native valve leaflets. In vitro cell culture demonstrated that BTS is non-cytotoxic, and cell alignment and proliferation behavior are influenced by the fiber orientation of the electrospun scaffold. Hemodynamic tests showed that the effective orifice area and regurgitation rate of the artificial valve can meet the requirements of the ISO 5840-2 standard. In summary, the tailored BTS mimicking natural microstructures exhibits isotropic mechanical properties similar to those of native leaflets, along with excellent biocompatibility, demonstrating great potential as a scaffold for TEHVs. • Bioinspired trilayer scaffolds (BTS) with native-like structures are fabricated for heart valve constructs. • BTS show J-curve stress-strain behavior and anisotropy similar to native valves. • BTS with high biocompatibility show great potential as scaffolds for TEHVs.