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.

Interfaces within biological tissues not only connect different regions but also contribute to the overall functionality of the tissue. This is especially true in the case of the aortic heart valve. Here, melt electrowriting (MEW) is used to engineer complex, user‐defined, interfaces for heart valve scaffolds. First, a multi‐modal imaging investigation into the interfacial regions of the valve reveals differences in collagen orientation, density, and recruitment in previously unexplored regions including the commissure and inter‐leaflet triangle. Overlapping, suturing, and continuous printing methods for interfacing MEW scaffolds are then investigated for their morphological, tensile, and flexural properties, demonstrating the superior performance of continuous interfaces. G‐codes for MEW scaffolds with complex interfaces are designed and generated using a novel software and graphical user interface. Finally, a singular MEW scaffold for the interfacial region of the aortic heart valve is presented incorporating continuous interfaces, gradient porosities, variable layer numbers across regions, and tailored fiber orientations inspired by the collagen distribution and orientation from the multi‐modal imaging study. The scaffold exhibits similar yield strain, hysteresis, and relaxation behavior to porcine heart valves. This work demonstrates the ability of a bioinspired approach for MEW scaffold design to address the functional complexity of biological tissues.

Three-dimensional (3D) printing plays an important role in cardiovascular disease through the use of personalised models that replicate the normal anatomy and its pathology with high accuracy and reliability. While 3D printed heart and vascular models have been shown to improve medical education, preoperative planning and simulation of cardiac procedures, as well as to enhance communication with patients, 3D bioprinting represents a potential advancement of 3D printing technology by allowing the printing of cellular or biological components, functional tissues and organs that can be used in a variety of applications in cardiovascular disease. Recent advances in bioprinting technology have shown the ability to support vascularisation of large-scale constructs with enhanced biocompatibility and structural stability, thus creating opportunities to replace damaged tissues or organs. In this review, we provide an overview of the use of 3D bioprinting in cardiovascular disease with a focus on technologies and applications in cardiac tissues, vascular constructs and grafts, heart valves and myocardium. Limitations and future research directions are highlighted.