Periodic Reporting for period 3 - REPAIR (RESTORING CARDIAC MECHANICAL FUNCTION BY POLYMERIC ARTIFICIAL MUSCULAR TISSUE)
Periodo di rendicontazione: 2023-09-01 al 2025-05-31
Heart Failure (HF) and Atrial Fibrillation (AF) are both associated with impairment of cardiac mechanical function. To assist ventricular contractility in HF, left ventricular assist devices (LVADs) have been developed and demonstrated able to reduce mortality in patients awaiting transplantation, but enormous disadvantages largely limit their long-term use. In parallel, promising devices to mechanically assist atrial contractile function have been successfully tested in large animals but never reached the clinical use.
Our idea was to exploit smart materials to support the cardiac mechanical function. Among smart materials, liquid crystalline elastomers (LCEs) are able to respond to external stimuli in a reversible manner to generate movement or tension.
REPAIR has developed a novel LCE-based artificial muscle that under external light stimulation is able to enhance cardiac muscle contraction. As a first step, a thorough coordinated effort was dedicated to the improvement of the starting material: its implementation required a strategy aimed to integrate the LCE stuff with light sources.
As a second step, multiple LCE-LEDs contractile units were assembled and engineered in an original device, the biomimetic contractile unit (BCU), integrating the responsive material with the light stimulus (e.g. a miniLED matrix): Finally,after a complete set of advanced tests in electronic workshops, the BCU underwent ex-vivo preliminary experiments on large animal hearts. Overall, the BCU demonstrates, for the first time, the capability of developing measurable tension on atrial tissue, paving the way to the future exploitation of such an innovative device for supporting contractility of human tissues.
Our idea was to exploit smart materials to support the cardiac mechanical function. Among smart materials, liquid crystalline elastomers (LCEs) are able to respond to external stimuli in a reversible manner to generate movement or tension.
REPAIR has developed a novel LCE-based artificial muscle that under external light stimulation is able to enhance cardiac muscle contraction. As a first step, a thorough coordinated effort was dedicated to the improvement of the starting material: its implementation required a strategy aimed to integrate the LCE stuff with light sources.
As a second step, multiple LCE-LEDs contractile units were assembled and engineered in an original device, the biomimetic contractile unit (BCU), integrating the responsive material with the light stimulus (e.g. a miniLED matrix): Finally,after a complete set of advanced tests in electronic workshops, the BCU underwent ex-vivo preliminary experiments on large animal hearts. Overall, the BCU demonstrates, for the first time, the capability of developing measurable tension on atrial tissue, paving the way to the future exploitation of such an innovative device for supporting contractility of human tissues.
The REPAIR consortium has developed novel LCE-based materials with improved efficiency. Newly synthesized molecules were obtained by inserting a bulky group in the LC core through optimized synthetic procedure, leading to materials showing improved elasticity and active and passive tensions. Furthermore, a biomimetic contractile unit (BCU) integrating the responsive material with the light stimulus (e.g. a miniLED matrix) was built. Preliminary tests on large mammals were performed ex-vivo.
Exploitation of our BCU, based on an unprecedented assembly of LCE and LED multistructures, requires further ex vivo experiments to be optimized as an epicardially-placed device to assist atrial contraction; these tests are ongoing to implement a patent application draft to be re-submitted for evaluation to one of the consortium universities’ TTO. In parallel, in silico approaches have been used to simulate its use in different settings - namely arteries or veins - to correct arterial or venous insufficiency.
About dissemination, different results were obtained:
- “The Secrets of Light” in 2022 (https://www.raiplay.it/video/2022/07/I-segreti-della-luce---Superquark-06072022-a3efc25e-1462-4ef4-a4ac-2e6e8879ff9f.html(si apre in una nuova finestra)) as a part of the popular Italian scientific programme Superquark at prime time
- dedicated professional video, recorded at Unifi, available through the website and the social media (https://youtu.be/UKDulipbvdQ)(si apre in una nuova finestra);
- Press releases and promotional articles: Specific Polymers produced two newsletters, a full one and an insert, dedicated to REPAIR, reaching 10,000 recipients.
- Publications: 32 papers were published open-access in international peer-reviewed journals by the consortium.
- More than 20 national and international meetings and conferences attended by the consortium members.
- REPAIR was presented at BRIGHT NIGHT in Florence in 2024 and at Festival della Scienza in Genova 2025.
Exploitation of our BCU, based on an unprecedented assembly of LCE and LED multistructures, requires further ex vivo experiments to be optimized as an epicardially-placed device to assist atrial contraction; these tests are ongoing to implement a patent application draft to be re-submitted for evaluation to one of the consortium universities’ TTO. In parallel, in silico approaches have been used to simulate its use in different settings - namely arteries or veins - to correct arterial or venous insufficiency.
About dissemination, different results were obtained:
- “The Secrets of Light” in 2022 (https://www.raiplay.it/video/2022/07/I-segreti-della-luce---Superquark-06072022-a3efc25e-1462-4ef4-a4ac-2e6e8879ff9f.html(si apre in una nuova finestra)) as a part of the popular Italian scientific programme Superquark at prime time
- dedicated professional video, recorded at Unifi, available through the website and the social media (https://youtu.be/UKDulipbvdQ)(si apre in una nuova finestra);
- Press releases and promotional articles: Specific Polymers produced two newsletters, a full one and an insert, dedicated to REPAIR, reaching 10,000 recipients.
- Publications: 32 papers were published open-access in international peer-reviewed journals by the consortium.
- More than 20 national and international meetings and conferences attended by the consortium members.
- REPAIR was presented at BRIGHT NIGHT in Florence in 2024 and at Festival della Scienza in Genova 2025.
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.
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.