Models and biomaterials for ageing cardiac tissue regeneration

The ageing of heart is associated with a lot of structural and functional changes; the most relevant of them are a great loss of cardiomyocytes, post-mitotic cells, and an increase in systolic blood pressure, due to blood vessel age-related modifications1. Transforming growth factor-β1 expression, that stimulates the production of collagen, increases with pressure overload, while metalloproteinases, responsible for collagen degradation, are down-regulated. This process brings to an increase of type I collagen and collagen cross-linking, thus causing heart fibrosis1. Currently, models able to reproduce the physio-pathological conditions of aged heart lack. Tissue Engineering strategies could be useful to develop in vitro dynamic models simulating ageing hearts, while respecting the three Rs ("Replacement, Refinement, Reduction") of animal testing. In this work, several polyurethane-based scaffolds were fabricated through the Thermally Induced Phase Separation technique to simulate both health young heart and aged heart. The differences between the two models mainly refer to mechanical properties and micro-architecture, having the aged heart model a major rigidity and smaller pore diameter. Different polymers and polymer solution concentrations were used, depending on the degree of ageing to simulate. The mechanical properties of the fabricated scaffolds were investigated through tensile tests, while scanning electron microscopy (SEM) was used to examine their micro-architecture. The elastic modulus of the structures was in the order of a few MPa, with slight differences between the young and aged-heart simulating scaffolds. Pore size was calculated from SEM images and resulted in the range of tens-hundreds of µm. The scaffolds were also biologically characterized by in vitro cell tests, with non-cardiac cells, showing a good biocompatibility. Biological static and dynamic tests with rat cardiomyocytes have been further planned, with the aim to check the suitability of the fabricated scaffolds to model the heart