Heart valves are characterized to be highly flexible yet tough, and exhibit complex deformation characteristics such as nonlinearity, anisotropy, and viscoelasticity, which are, at best, only partially recapitulated in scaffolds for heart valve tissue engineering (HVTE). These biomechanical features are dictated by the structural properties and microarchitecture of the major tissue constituents, in particular collagen fibers. In this study, the unique capabilities of melt electrowriting (MEW) are exploited to create functional scaffolds with highly controlled fibrous microarchitectures mimicking the wavy nature of the collagen fibers and their load‐dependent recruitment. Scaffolds with precisely‐defined serpentine architectures reproduce the J‐shaped strain stiffening, anisotropic and viscoelastic behavior of native heart valve leaflets, as demonstrated by quasistatic and dynamic mechanical characterization. They also support the growth of human vascular smooth muscle cells seeded both directly or encapsulated in fibrin, and promote the deposition of valvular extracellular matrix components. Finally, proof‐of‐principle MEW trileaflet valves display excellent acute hydrodynamic performance under aortic physiological conditions in a custom‐made flow loop. The convergence of MEW and a biomimetic design approach enables a new paradigm for the manufacturing of scaffolds with highly controlled microarchitectures, biocompatibility, and stringent nonlinear and anisotropic mechanical properties required for HVTE.

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We present a design rationale for stretchable soft network composites for engineering tissues that predominantly function under high tensile loads. The convergence of 3D-printed fibers selected from a design library and biodegradable interpenetrating polymer networks (IPNs) result in biomimetic tissue engineered constructs (bTECs) with fully tunable properties that can match specific tissue requirements. We present our technology platform using an exemplary soft network composite model that is characterized to be flexible, yet ∼125 times stronger (E = 3.19 MPa) and ∼100 times tougher (W = ∼2000 kJ m) than its hydrogel counterpart.

Heart valve tissue engineering (HVTE) aims to provide living autologous heart valve implants endowed with regenerative capabilities and life-long durability. However, fabrication of biomimetic scaffolds capable of providing the required functionality in terms of mechanical performance and tunable porosity to enable cellular infiltration remains a major challenge. Here, the additive manufacturing of bioinspired, spatially heterogeneous, tubular scaffolds enclosing the leaflets, inter-leaflet triangles, and their interface for in situ HVTE using melt electrowriting (MEW) is demonstrated. The innovative platform enables the digital fabrication of scaffolds with ad hoc architecture (e.g., tunable location, specific fiber pattern, and orientation) and customizable geometry via a custom-made control software. The user-friendly interface allows for the definition of areas of the scaffold with specific patterns to obtain properties such as tunable J-shaped stress-stain curve and anisotropy typical of the heart valve leaflet, compliant inter-leaflet triangles, and reinforced curvilinear boundary between them. Heterogeneous, tubular, heart valve MEW scaffolds are then embedded with a microporous elastin-like recombinamer (ELR) hydrogel to develop a soft-network composite favoring cell infiltration and ensuring hemocompatibility. The acute systolic hemodynamic functionality of the MEW/ELR composite satisfies the ISO 5840 requirements, under aortic and pulmonary conditions.