Design and fabrication of auxetic scaffolds for cardiac regeneration

Heart failure resulting from myocardial infarction (MI) remains a leading cause of global mortality, despite recent advancements in its treatment. Current therapeutic approaches aim to stabilize scars, reduce infarct expansion, and mitigate ventricular wall stress to improve patient outcomes. Cardiac tissue engineering (CTE) offers a promising strategy for repairing and regenerating damaged myocardium post-MI. Biological scaffolds play a pivotal role in CTE by mimicking native tissue environment, facilitating cell adhesion, alignment, and organization into functional cardiac patches. However, traditional scaffolds often fail to replicate the unique mechanical properties of the myocardium, such as its negative Poisson's ratio, critical for withstanding daily mechanical demands. This thesis explored the potential of auxetic metamaterials in biomedical applications, specifically for cardiac scaffold design. The configuration of unit cells, which are the fundamental building blocks of metamaterials, significantly influences their overall mechanical properties at a larger scale. Auxetic metamaterials are noteworthy for their unique ability to expand laterally when stretched longitudinally (negative Poisson's ratio). Hence, auxetic structures, thanks to their negative Poisson's ratio, resemble the mechanical behavior of myocardial tissue, offering superior shear and indentation resistance. Based on these premises, the objective of this work was to design and fabricate 3D auxetic scaffolds via Fused Deposition Modeling (FDM) of a custom-made thermoplastic poly(ester urethane) (PUR) and a commercially available poly(caprolactone)/poly(L-lactic acid) (PCL/PLLA) elastic co-polymer. The PUR was based on poly(ɛ-caprolactone) diol, 1,6-hexamethylene diisocyanate, and a linear aliphatic chain extender (1,12-dodecanediol). The PUR chemical characterization was carried out using Infrared (IR) spectroscopy and Size Exclusion Chromatography (SEC), confirming its successful synthesis. Nine different scaffold geometries (i.e., Arrowhead, Sinusoidal, Hexagon, Hybrid, Star, Tetrachiral, Rotating Square, Lozenge Grid, Square Grid) were explored to identify key structural parameters influencing auxeticity. After the optimal parameters for each geometry were selected, auxetic scaffolds were designed using a CAD software. A custom slicing algorithm was then employed to convert the 3D models into printable paths. Mechanical testing, including tensile tests and finite element modeling (FEM), was used to evaluate structural parameters such as Poisson's ratio, elastic modulus and toughness, crucial for assessing scaffold performance. The results indicated high printing fidelity across all complex geometries, except for the rotating square, which displayed a positive Poisson’s ratio attributed to manufacturing defects. All other geometries exhibited a Negative Poisson’s ratio. Tensile tests revealed that the auxetic patches displayed superior elasticity and strain capacity compared to what is typically required for the physiological activity of cardiac tissue. Both experimental and FEM analyses demonstrated consistent predictions of the deformation behavior characteristic of auxetic structures. By investigating different geometric designs of auxetic structures, this study provided relevant insight into the significance of Poisson's ratio in the development of heart patches, potentially paving the way for effective treatments that improve survival rates and quality of life for myocardial infarcted patients.