Periodic Reporting for period 2 - REPAIR (RESTORING CARDIAC MECHANICAL FUNCTION BY POLYMERIC ARTIFICIAL MUSCULAR TISSUE)
Berichtszeitraum: 2022-03-01 bis 2023-08-31
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 revolutionary idea to solve these clinical challenges is to exploit smart materials to support or restore 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.
The REPAIR Consortium has recently developed a novel LCE-based artificial muscle that under external light stimulation is able to enhance cardiac muscle contraction. These results pave the way for the development of a novel generation of cardiac assist devices. We will first develop a mechanical performant and energetically efficient LCE material that, integrated with light sources (μLED array), will result in fundamental biomimetic contractile units to be structured in a suturable, remote controlled contractile tissue.
The LCE-μLEDs contractile tissue will be exploited to develop a new generation of cardiac assist devices (e.g. ventriculoplasty patches, aortic rings for diastolic counterpulsation and epicardial bundles for atrial contraction assistance) and test the effects of their acute implantation in large mammals (open-chest sacrifice experiments) and human explanted hearts. Among LCE-device features: they will be self- contracting, low weight, associated with low thromboembolic risk, and most importantly, they will rely on a control unit that can modulate the exerted force providing the fist “tunable” cardiac assist device ever developed.
Our revolutionary idea to solve these clinical challenges is to exploit smart materials to support or restore 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.
The REPAIR Consortium has recently developed a novel LCE-based artificial muscle that under external light stimulation is able to enhance cardiac muscle contraction. These results pave the way for the development of a novel generation of cardiac assist devices. We will first develop a mechanical performant and energetically efficient LCE material that, integrated with light sources (μLED array), will result in fundamental biomimetic contractile units to be structured in a suturable, remote controlled contractile tissue.
The LCE-μLEDs contractile tissue will be exploited to develop a new generation of cardiac assist devices (e.g. ventriculoplasty patches, aortic rings for diastolic counterpulsation and epicardial bundles for atrial contraction assistance) and test the effects of their acute implantation in large mammals (open-chest sacrifice experiments) and human explanted hearts. Among LCE-device features: they will be self- contracting, low weight, associated with low thromboembolic risk, and most importantly, they will rely on a control unit that can modulate the exerted force providing the fist “tunable” cardiac assist device ever developed.
The REPAIR consortium has recently developed novel LCE-based materials with improved efficiency. The composition of the reference material was modified by changing the dye, leading to a more performant material, while the substitution of the cross-linker is still under evaluation. 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 under evaluation in terms of balance between 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. Simulations and experiments to substitute the array of miniLED with an array of micro-LED and towards the generation of the uBCU are still ongoing.
Our revolutionary idea is to exploit smart materials to support or restore the cardiac mechanical function. So far many attempts to create materials or devices have failed in reproducing the natural muscle function and regulation. In this regard biocompatible polymers able to work as actuators are gaining interest. Among smart materials liquid crystalline elastomers (LCEs) are able to respond to external stimuli in a reversible manner to generate movement or tension. However even if LCEs are commonly called artificial muscles their application in biology is still limited to a few examples. The implementation of contraction assist devices based on LCEs technology may revolutionize the current therapeutic approaches to cardiac conditions characterized by ventricular or atrial mechanical failure.
The results of REPAIR are expected to profoundly impact on the treatment of heart failure: innovative devices aimed at enhancing the life quality for people with severe chronic health conditions requiring frequent hospitalization while waiting for cardiac transplantation. REPAIR’s objectives address the urgent need to improve the quality sustainability lifetimes of implantable cardiac assist devices thus offering a breakthrough in the medical armamentarium of cardiac devices and mitigating the impact of life-threatening disease on the healthcare systems.
REPAIR will also impact innovation capacity and final delivery of the project results to the market thanks to the unique contribution of partners from different countries, company size types, and sectors that will work collaboratively ensuring a breakthrough. The deliveries of the project will benefit the innovation ecosystem related to mini-invasive medical devices: industry technology and material developers and European health care systems.
The availability of mini-invasive devices will drastically improve the quality of life of patients allowing them to recover toward a full social and working activity. Besides the reduced dimensions REPAIR devices will be based on fully biocompatible and easily recycled material and on low-power LED technology. The possibility to further improve cardiac patches by independently generating power thanks to dynamic technology generating electricity from the movement will reduce the cost and risk and environmental impact intrinsic to battery change (e.g. infections and over-use of antibacterial drugs) and move toward lifelong devices.
The results of REPAIR are expected to profoundly impact on the treatment of heart failure: innovative devices aimed at enhancing the life quality for people with severe chronic health conditions requiring frequent hospitalization while waiting for cardiac transplantation. REPAIR’s objectives address the urgent need to improve the quality sustainability lifetimes of implantable cardiac assist devices thus offering a breakthrough in the medical armamentarium of cardiac devices and mitigating the impact of life-threatening disease on the healthcare systems.
REPAIR will also impact innovation capacity and final delivery of the project results to the market thanks to the unique contribution of partners from different countries, company size types, and sectors that will work collaboratively ensuring a breakthrough. The deliveries of the project will benefit the innovation ecosystem related to mini-invasive medical devices: industry technology and material developers and European health care systems.
The availability of mini-invasive devices will drastically improve the quality of life of patients allowing them to recover toward a full social and working activity. Besides the reduced dimensions REPAIR devices will be based on fully biocompatible and easily recycled material and on low-power LED technology. The possibility to further improve cardiac patches by independently generating power thanks to dynamic technology generating electricity from the movement will reduce the cost and risk and environmental impact intrinsic to battery change (e.g. infections and over-use of antibacterial drugs) and move toward lifelong devices.