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

Project description

Tissue-engineered heart valves

The mitral valve is responsible for maintaining proper blood flow in the heart in one direction, from the left atrium to the left ventricle. When the mitral valve doesn’t work properly, the heart does not pump enough blood, causing fatigue and shortness of breath. In severe cases, prosthetic heart valves are used to replace dysfunctional valves. The EU-funded BIOMITRAL project will focus on tissue engineered valves that have the capacity to also regenerate the endogenous tissue, facilitate remodelling, and grow with the patient. Researchers will develop a polymer-based mitral valve that functions according to the native physiological mechanism and exhibits enhanced functional 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.

Host institution

FONDAZIONE RI.MED
Net EU contribution
€ 1 880 506,25
Address
VIA BANDIERA 11
90133 Palermo
Italy

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Region
Isole Sicilia Palermo
Activity type
Research Organisations
Links
Total cost
€ 1 880 506,25

Beneficiaries (3)