3D Bioprinting of Heart Valves

Valvular heart diseases (VHDs) are a rapidly growing cause of global mortality and morbidity, with an estimated prevalence of 2.5% worldwide. Despite its significance, the current gold standard for VHDs treatment is to replace the diseased and malfunctioning valves with a homograft, bioporosthetic valve, or a mechanical valve. Although life-saving potential, these substitutes present several inherent limitations such as limited availability, immune rejection, and thrombogenicity. These complications render existing solutions suboptimal and highlight the urgent need for alternative therapeutic strategies. Tissue engineering has emerged as a promising avenue to overcome these challenges; however, its application in heart valve replacement remains significantly underexplored compared to other tissue types. This thesis investigates the potential of tissue engineering through the integration of biopolymers, 3D (bio)printing technologies, and stem cells to develop next-generation tissue-engineered heart valves (TEHVs) that address the shortcomings of current valve replacement therapies. Throughout this thesis, initially, a novel composite ink was formulated for extrusion-based 3D printing. This ink demonstrated the capacity to fabricate geometrically complex, support-free, human-sized TEHVs. Comprehensive evaluations, including mechanical, structural, and functional evaluations revealed that the printed valves exhibit key features necessary for further development as clinically viable implants. Building upon these findings, the next phase of the research focused on the development and characterization of a new photosensitive polysaccharide derived from quince seed mucilage. This material was engineered for light-induced crosslinking and subsequently incorporated with other synthetic and natural biopolymers to formulate a novel bioink optimized for digital light processing (DLP) 3D printing. Using this ink, TEHVs were fabricated and evaluated to assess their structural integrity, biocompatibility, and functional performance under physiological conditions, demonstrating their suitability for future in vivo investigations. In summary, this work presents two distinct, yet complementary, bioinks and printing strategies for the fabrication of TEHVs. Both approaches yielded promising results in terms of mechanical resilience, bioactivity, and hemodynamic function, positioning them as strong candidates for further preclinical validation and eventual clinical translation.