Biomimetic materials for novel cardiac regeneration approaches

The quest for novel biomaterials to promote cell structural and functional maturation for cardiac tissue regeneration has emphasized a need to create microenvironments with physiological features. Substrate stiffness constitutes a structural property of crucial importance in the field of tissue engineering and many studies have shown how cardiac cells sense the rigidity of the substrate on which they grow. In this work, we focused on the relevance of substrates mimicking cardiac extracellular matrix (cECM) rigidity for the understanding of the complex interplay between the extracellular and intracellular compartments. Among the most promising biomaterials, Liquid Crystalline Elastomers (LCEs) represent a novel class of polymers previously investigated both as artificial muscles for biomedical purposes and dynamic cell scaffolds. The development of new smart materials which can provide bioactive cues to control and regulate cell fate has been recently encouraged. Indeed, mechanical cues play a significant role in maintaining cell and tissues/organs functions and, in this respect, cell models and substrate stiffness appear as intriguing tools for the investigation of cECM-cell interactions both in physiological and pathological conditions. From the perspective of materials, we have explored the fabrication of biomimetic patterned substrates to direct human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) growth and evaluate their effect on cell functional properties. In the field of regenerative medicine, the advent of hiPSC-CMs has paved the way for a patient-specific therapy but the development of more mature hiPSC-CMs is still needed. Promising approaches that have begun to be investigated include long-term culture, mechanical loading, 3-dimensional tissue engineering and, above all, the use of dynamic scaffolds to boost cell maturation by giving a mechanical stimulus. Finally, with the aim of creating an effective dynamic cell substrate, we have introduced the design of the first prototype of LCE-based biomimetic contractile unit by optimizing a miniaturization of the mechanical device. The functional properties of the contractile apparatus have been investigated and then modulated to closely reproduce the features of native myocardium. Overall, in this work we have provided an overview of some functional aspects of biomaterials which are considered of key relevance in different biomedical fields to elucidate how recent advances may impact future tissue engineering applications.