Al prof. Pasquale Sacco del Dipartimento di Scienze della Vita dell’Università degli Studi di Trieste, sono stati assegnati 1.65 milioni di Euro come finanziamento del progetto intitolato “Reversal of cardiac fibrosis and promotion of tissue regeneration through controlled SOFTENing of the extracellular matrix milieu” che si propone di studiare e trovare nuove strategie per riparare i danni cardiaci.

Le malattie cardiovascolari rappresentano una delle principali sfide sanitarie in Europa, con costi annui di 282 miliardi di euro (circa 630 euro per cittadino e l'11% della spesa sanitaria totale). Il cuore umano adulto non si rigenera dopo un danno, a differenza di ciò che accade nel piccolo pesce di acqua dolce chiamato “Zebrafish”, che recupera completamente la funzionalità entro 60-90 giorni grazie ai cardiomiociti sopravvissuti che entrano in proliferazione e producono nuovo tessuto muscolare, ricostruendo l'area danneggiata senza fibrosi permanente.

Con il progetto SOFTEN il prof. Sacco propone di costruire biomateriali bioispirati che mimano il comportamento delle cellule cardiache del Zebrafish, utilizzando reti di idrogel regolabili per colture 2D e 3D di fibroblasti e cardiomiociti derivati da cellule staminali pluripotenti indotte (iPSC).

Attraverso un approccio multidisciplinare – design di materiali, chimica polimerica e biologia cellulare – SOFTEN fornirà informazioni fondamentali sulla meccanobiologia cardiaca, sulla fibrosi e sulla rigenerazione, aprendo la strada a nuove strategie terapeutiche per risolvere questi gravi problemi di salute.

Questo ambizioso progetto ha ottenuto un finanziamento di circa 1.650.000 euro dal Fondo Italiano per la Scienza del MUR.

Abstract: Cardiovascular diseases are a major health problem throughout Europe today, which cost the Europe economy 282 billion Euro/year, corresponding to an average cost of 630 Euro/citizen and 11% of Europe-health expenditure. After an injury, the adult human heart does not have the ability to renew itself. However, it is known that teleost fishes such as Zebrafish can regenerate the heart after a transient softening of the cardiac extracellular matrix (ECM), which temporarily restores cardiomyocyte division and activates fibroblasts. Furthermore, cellular and molecular mechanisms have deciphered the ability of the mammalian heart to regenerate in the short window of time immediately after birth. Biomaterials currently used as model of cardiac ECM have provided limited insights into cell mechanobiology due to their unnatural, purely elastic nature, wrong rigidity and, mostly, inability to provide controlled softening behaviour. Thus, advanced bioinspired cardiac ECM mimics are urgently needed to achieve a real breakthrough in this field. SOFTEN is an ambitious project that proposes the innovative concept of mimicking the transient softening ability of the cardiac ECM exploited by the Zebrafish to regenerate its heart. Experimental approaches in this direction are groundbreaking, but they are still in their infancy, thus SOFTEN is of high-risk/high-gain nature. Therefore, in the first instance the Applicant’s group will leverage recent discoveries to develop hydrogel networks with adjustable softening capacity. The second focus is to use these biomaterials as cardiac ECM mimics suitable for 2D and 3D cultures of fibroblasts and cardiomyocytes derived from induced pluripotent stem cells (iPSC) to advance current knowledge of cardiac fibrosis and heart regeneration. To achieve these milestones, a multidisciplinary approach involving material design, polymer chemistry and in vitro cellular and molecular biology methods is required to provide real insights into basic science and, possibly, therapeutic strategies for these unresolved health problems. In addition to these main objectives, SOFTEN will also achieve several intermediate goals by providing fundamental insights and crucial new elements to push the frontiers of cardiac cell mechanobiology beyond the current state of the art.