Periodic Reporting for period 1 - REBORN (REMODELLING OF THE INFARCTED HEART: PIEZOELECTRIC MULTIFUNCTIONAL PATCH ENABLING THE SEQUENTIAL RELEASE OF THERAPEUTIC FACTORS)
Periodo di rendicontazione: 2023-01-01 al 2024-07-31
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 and control the temporal sequence of release of therapeutics and to enhance their penetration into the heart tissue, in order to create a healthy regenerative microenvironment.
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 and control the temporal sequence of release of therapeutics and to enhance their penetration into the heart tissue, in order to create a healthy regenerative microenvironment.
During the first period the following work has been performed:
* A cardiac patch has been successfully produced featuring aligned nanofibers and piezoelectric properties. The patch is biocompatible and can be produced with a process that do not involve toxic solvents.
* A platform of biocompatible, engineered smart carriers able to incorporate and release, upon controlled ultrasound stimulation various drugs have been successfully developed.
* 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), in REBORN we have developed two ultrasound systems (low and high frequency range respectively) to allow a broad range of parameters to be explored in order to optimize the US triggered release.
* Extracellular vesicles enriched with mi-RNA were also successfully prepared and characterised in order to stimulate cardiomyocytes.
* The carriers and the extracellular vesicles are meant to be incorporated into the cardiac patch: this activity already started and it is still on going.
* The development of an 3D advanced in vitro test set-up mimicking a hearth chamber is currently under development and is leveraged by the use of an innovative, patented biofabrication technique available at one of the REBORN partner.
* A cardiac patch has been successfully produced featuring aligned nanofibers and piezoelectric properties. The patch is biocompatible and can be produced with a process that do not involve toxic solvents.
* A platform of biocompatible, engineered smart carriers able to incorporate and release, upon controlled ultrasound stimulation various drugs have been successfully developed.
* 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), in REBORN we have developed two ultrasound systems (low and high frequency range respectively) to allow a broad range of parameters to be explored in order to optimize the US triggered release.
* Extracellular vesicles enriched with mi-RNA were also successfully prepared and characterised in order to stimulate cardiomyocytes.
* The carriers and the extracellular vesicles are meant to be incorporated into the cardiac patch: this activity already started and it is still on going.
* The development of an 3D advanced in vitro test set-up mimicking a hearth chamber is currently under development and is leveraged by the use of an innovative, patented biofabrication technique available at one of the REBORN partner.
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.
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.