The results of REPAIR progress the state of the art on Liquid Crystal Elastomers (LCEs) by having introduced new monomers and crosslinked, resulting in more performant materials, synthesis and production scale-up, both by 3D printing and film production techniques. Such implemented materials were used for scaling up the capability to produce macro-forces, a result that has never been attempted so far. The development of a complex device, requiring the integration of an European consortium bringing together engineers, physicists, chemistrians, and physicians, led to the design and proof-of-concept of a Biomimetic Contractile Unit (BCU), proved capable to produce 1-Newton force, overcoming - for the first time - the intrinsic limitations of this technology. As a matter of fact, before REPAIR, LCE manufacts were employed for generating force in the nano- or micro-scale. For the first time, these results indicate that LCE technology is capable of generating macroscopic forces, opening the way for next applications ex-vivo for restoring contractile function of the heart (and beyond). Although not sufficient for the ventricular muscle, such a force production was sufficient to assist the atrial muscle contraction or to support contractile insufficiency of other tissue, e.g. veins or arteries. Meantime, REPAIR have successfully demonstrated the foundational feasibility of epicardial mechanical atrial assist, by the development and validation of a simplified pneumatic actuator that enabled extensive physiological investigations, and an LCE-based atrial assist device was successfully developed. To further support this perspective and the exploitation of LCE/LED devices, a "virtual heart" modelling software was developed in collaboration with Francesco Regazzoni (Politecnico di Milano), based on a validated numerical model of the cardiovascular system. The computational model was calibrated to assess how this device can affect left ventricular preload, providing valuable insights into the mechanisms and systemic effects of preload variation through atrial mechanical assistance.
Another, experimental value of the REPAIR project consists in the biological assessment of LCE-based constructs as dynamic scaffolds to support and stimulate the maturation and alignment of cardiomyocytes derived from patient-specific pluripotent stem cells (hiPSC), to be used for personalized engineered cardiac tissue.
REPAIR had a great impact on young participants. Master students (11) and PhDs (8) are actively involved in daily co-working, in presence and weekly on-line (Webex meetings). Their participation and personal contribution were always taken into consideration to attain the expected result. This approach, in particular the constant interfacing between young/experienced researchers, led to a remarkable improvement in LCE manufacturing (3D printing) and LED refinement. Besides young post-docs, several Master and PhD students reported their work in thesis and papers - published, in preparation or just submitted.
REPAIR resulted in two innovative Bio-Contractile Units (BCUs) demonstrators. These demonstrators are founded on a sophisticated multilayer LED/LCE assembly, showcasing the capacity to generate substantial macroscopic forces in the range of 1-2N. This crucial step was attained thanks to original, ground-breaking manufacturing and assembly solutions. Although being aware of the challenges to further improve and test these prototypes in situ, these results are extremely encouraging in view of the innovative bio-mechanical approach to a real and so far, untested solution to clinical need.
