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Engineering the mitral valve: bioinspired control of structure and function for enhanced in vivo performance

Descrizione del progetto

Valvole cardiache di tessuto ingegnerizzato

La valvola mitrale è responsabile del mantenimento del corretto flusso di sangue nel cuore in una direzione, dall’atrio sinistro al ventricolo sinistro. Quando la valvola mitrale non funziona correttamente, il cuore non pompa abbastanza sangue, e ciò causa affaticamento e dispnea. Nei casi più gravi le valvole disfunzionali sono sostituite da protesi valvolari cardiache. Il progetto BIOMITRAL, finanziato dall’UE, si concentrerà sulle valvole in tessuto ingegnerizzato in grado di rigenerare anche il tessuto endogeno, facilitare il rimodellamento e crescere insieme al paziente. I ricercatori svilupperanno una valvola mitrale a base di polimeri che funziona secondo il meccanismo fisiologico nativo e offre prestazioni funzionali migliorate.

Obiettivo

Tissue Engineered Heart Valves (TEHVs) can restore function in the pulmonary and aortic positions and have shown capacity for tissue regeneration and growth in pre-clinical models. Yet, this concept has not been extended to the Mitral Valve (MV), whose pathologies affect >25% of the valve disease patients in Europe. In this proposal, we introduce a bio-inspired design methodology and bioprocessing technology to engineer BIOMITRAL: a polymeric, stent-less, tissue engineered MV that recapitulates native structure-function. Key to our approach is the engineering of MV leaflets and chordal apparatus. In the native MV, this set of tendon-like appendages mechanically connects the leaflets to the left ventricle (LV) and allows for harmonization of the valve kinematics, coaptation and ventricle contractile dynamics. Commercial MV prostheses used for MV replacement, as well as most existing TEHVs are mounted on synthetic stents that lack of this important structure and consequently neglect this physiological mechanism. In addition, non-degradable stents cannot adapt to patient's growth, de-facto negating a key advantage in TEHVs. Our specific hypothesis is that recapitulating native leaflet structure-function and incorporating engineered chordal apparatus will lead to an engineered MV with enhanced functional and remodeling performances. To verify our hypothesis, we will: Aim 1. Characterize the structure-function of freshly isolated human valve tissue and use the derived properties to fabricate stented (control) and stentless BIOMITRAL prototypes; Aim 2. Assess prototypes mechanics and kinematics in silico via finite element modeling and in vitro in a pulse duplicator; Aim 3. Evaluate BIOMITRAL in vivo functional performance and assess remodeling in a chronic ovine model. Engineering a “living” MV with bioinspired leaflets and chordae that connect engineered leaflets with the LV is a revolutionary concept that can fundamentally transform the design of MV prostheses.

Meccanismo di finanziamento

ERC-COG - Consolidator Grant

Istituzione ospitante

FONDAZIONE RI.MED
Contribution nette de l'UE
€ 1 880 506,25
Indirizzo
VIA BANDIERA 11
90133 Palermo
Italia

Mostra sulla mappa

Regione
Isole Sicilia Palermo
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 1 880 506,25

Beneficiari (3)