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

Objective

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.

Call for proposal

ERC-2020-COG
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Host institution

FONDAZIONE RI.MED
Address
Via Bandiera 11
90133 Palermo
Italy
Activity type
Research Organisations
EU contribution
€ 1 880 506,25

Beneficiaries (3)

FONDAZIONE RI.MED
Italy
EU contribution
€ 1 880 506,25
Address
Via Bandiera 11
90133 Palermo
Activity type
Research Organisations
ISTITUTO MEDITERRANEO PER I TRAPIANTI E TERAPIE AD ALTA SPECIALIZZAZIONE SRL - ISMETT SRL
Italy
EU contribution
€ 91 250
Address
Discesa Dei Giudici 4
90133 Palermo
Activity type
Other
UNIVERSITA DEGLI STUDI DI PALERMO
Italy
EU contribution
€ 18 773,75
Address
Piazza Marina 61
90133 Palermo
Activity type
Higher or Secondary Education Establishments