REMODELLING OF THE INFARCTED HEART: PIEZOELECTRIC MULTIFUNCTIONAL PATCH ENABLING THE SEQUENTIAL RELEASE OF THERAPEUTIC FACTORS

Informations projet

REBORN

N° de convention de subvention: 101091852

DOI

10.3030/101091852

Date de signature de la CE 29 Novembre 2022

Date de début 1 Janvier 2023

Date de fin 31 Decembre 2026

Financé au titre de

• Digital, Industry and Space

Coût total

€ 4 050 412,50

Contribution de l’UE

€ 4 050 412,50

Coordonné par

POLITECNICO DI TORINO
Italy

Periodic Reporting for period 2 - REBORN (REMODELLING OF THE INFARCTED HEART: PIEZOELECTRIC MULTIFUNCTIONAL PATCH ENABLING THE SEQUENTIAL RELEASE OF THERAPEUTIC FACTORS)

Période du rapport: 2024-08-01 au 2025-12-31

Résumé du contexte et des objectifs généraux du projet

Despite the mortality rate decrease observed in the last two decades, cardiovascular diseases still account for 3.9 million deaths (45% of all deaths) in Europe each year. A significant proportion of them is due to myocardial infarction, the other major cause being stroke.
The mammalian heart has limited regenerative capacity being the least regenerative organ in the body and thus, in myocardial infarction, ischemic cardiac cells (e.g. cardiomyocytes) are permanently lost and replaced by fibrous tissue. This reparative response leads to severe cardiac structural and functional alterations - adverse remodelling – that often result in heart failure and death of the patient. One important contributing factor in the transition to heart failure is the formation of excessive fibrosis that increases ventricular stiffness, facilitates arrhythmias and contributes to organ dysfunction. Current solutions are not able to address this chain of events leading to the unmet clinical need that the REBORN project will address.
The project’s ambition is to provide a multifunctional, cardiac patch that, when translated to the clinic, is expected to significantly prevent heart failure in patients surviving an acute myocardial infarction, reducing mortality and enhancing their quality of life.
REBORN will respond to this unmet clinical need by means of a synergistic integration of multifunctional biomaterials and electrospinning technology to deliver a fibrous piezoelectric patch able to provide the full set of cues required to promote a functional heart tissue remodelling.
External ultrasonic stimulation will be exploited to trigger the release of therapeutics, to enhance their penetration into the heart tissue and to exert a positive effect on heart cells, in order to create a healthy regenerative microenvironment.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

During the first two reporting periods the following work has been performed:
* A platform of biocompatible, engineered smart carriers able to incorporate and release, upon controlled ultrasound stimulation various drugs have been successfully developed.
On these carriers a complete in vitro characterisation with macrophages, cardiac fibroblast a cardiomyocites have been performed with and without US stimulation.
* Different prototypes of cardiac patches have been successfully produced featuring aligned nanofibers and piezoelectric properties. The patches are biocompatible and can be produced with a process that do not involve toxic solvents.
The production process have been translated at TRL5.
* Extracellular vesicles enriched with mi-RNA were successfully prepared, characterised in order to stimulate cardiomyocytes and their incorporation on the patch achieved.
* Delivering strategy of the patch to the epicardium have been discussed and a few solutions defined.
* To overcome the limitations of the current ultrasound systems used for drug delivery experiments (e.g. unpredictable ultrasound (US) signal reaching the target and fixed frequency and intensity), two ultrasound systems (low and high frequency range respectively) have been developed to allow a broad range of parameters to be explored in order to optimize the US triggered release.
* The development of an 3D advanced in vitro test set-up mimicking a hearth chamber is at an advanced stage of development and is leveraged by the use of an innovative, patented biofabrication technique available at one of the REBORN partner.
* Health economic models have been developed to assess the value of the developed solutions.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

REBORN has made notable progress towards delivering scientific impact, specifically through the development of cutting-edge technologies that tackle critical gaps in current regenerative medicine, particularly in cardiac care. By addressing pressing healthcare challenges that affect millions of people worldwide, REBORN offers as well considerable societal benefits.
In relation to the work performed and the main achievements described above, 10 key exploitable results have been identified in the REBORN project. The results are currently under development, and more will be eventually identified with the progress of the project implementation. They are based on and include confidential information that cannot be made public at present. For each key exploitable result a clear pathway to industrial scalability, IP protection and possibly commercialization will be defined, offering new opportunities in medical device production, pharmaceutical development, and biotechnology services. The key steps necessary to ensure their uptake and success will be discussed amongst the REBORN partners, drawing, for each of them, the optimal exploitation beyond the project end. REBORN holds significant potential for economic and industrial impact through the commercialization of its key innovations.