biomimetic engineered chordae tendineae for valve repair and regeneration

Projektinformationen

BioChord

ID Finanzhilfevereinbarung: 101123370

DOI

10.3030/101123370

Projekt abgeschlossen

EK-Unterschriftsdatum 10 Juli 2023

Startdatum 1 Oktober 2023

Enddatum 31 März 2026

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 150 000,00

Koordiniert durch

FONDAZIONE RI.MED
Italy

Periodic Reporting for period 1 - BioChord (biomimetic engineered chordae tendineae for valve repair and regeneration)

Berichtszeitraum: 2023-10-01 bis 2026-03-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Mitral regurgitation affects over 24 million people worldwide and is frequently caused by elongation or rupture of the chordae tendineae (CT), specialized tendon-like structures that anchor the valve leaflets to the papillary muscles. CT are not merely passive collagenous components of the valvular apparatus but living, vascularized tissues that contribute to the structural integrity and biological homeostasis of the heart. These structural and functional characteristics are critical determinants of long-term surgical outcomes and must be considered in advancing CT replacement strategies. However, current surgical techniques have remained largely unchanged since the mid-1980s and rely on non-degradable expanded polytetrafluoroethylene (ePTFE) sutures, microporous, non-absorbable monofilaments that fail to replicate the hierarchical architecture and biomechanical behavior of native CT. As a result, while broadly adopted, these artificial chordae are still prone to long-term failure due to mechanical mismatch, fibrosis, calcification, and chronic inflammatory responses.
The BioChord project builds upon advances achieved within the ERC Consolidator Grant BIOMITRAL, which introduced a tissue-engineered mitral valve incorporating valve leaflets with a subvalvular apparatus. This Proof of Concept project aims to specifically develop and validate BioChord, a first-in-class, bioengineered, cell-free polymeric scaffold designed to recapitulate the hierarchical structure and mechanical function of native CT while promoting endogenous tissue regeneration. Leveraging on a proprietary mandrel-less electrodeposition technology that enables the fabrication of customizable, physiologically relevant constructs with demonstrated capacity for cellular infiltration and extracellular matrix deposition. BioChord is designed to initially restore mechanical continuity within the valve apparatus by replacing a damaged CT, and subsequently undergo the progressive biological integration, ultimately transforming into a functional, tendon-like structure capable of sustaining physiological mechanical load while transporting blood and nutrients.
The overall objective of this project is to advance BioChord from early-stage validation to translational readiness (TRL2 to TRL5) through optimization of manufacturing processes, demonstration of reproducible regenerative performance, and positioning as a stand-alone solution for valve repair. By addressing the fundamental limitations of current artificial chordae, this project seeks to shift the clinical paradigm from passive mechanical substitution toward active, biology-driven tissue regeneration.
The expected impact of this idea is substantial across multiple domains. Clinically, BioChord has the potential to enhance the durability and outcomes of valve repair, reducing complication rates and the need for re-intervention. Technically, it introduces a platform for bioinspired implants with applicability extending beyond cardiac surgery to tendon and soft tissue repair. Socio-economically, while addressing a niche application, the project may impact on the growing burden of valvular heart disease in aging populations, with the potential to reduce long-term healthcare costs and improve patient quality of life. Overall, BioChord represents a transformative step toward next-generation regenerative surgical and percutaneous mitral and tricuspid prostheses.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

During the reporting period, we conducted a comprehensive, multi-scale characterization and validation of BioChord technology.
First, we performed an in-depth comparative analysis of native CT from human, porcine, and ovine sources, the latter representing the principal preclinical models in cardiovascular research. Tissues were characterized in terms of mechanical properties (uniaxial tensile testing), cellular and extracellular matrix composition (histological assessment), and microstructure (scanning electron microscopy). These data established a quali-quantitative benchmark for the design of BioChord and informed us with the target range for the mechanical and structural parameters.
Second, we evaluated a range of polymeric materials, including both degradable, non-degradable, and blend formulations, to optimize scaffold performance. This work enabled validation of the fabrication approach across materials and refinement of process parameters to achieve reproducible constructs. In parallel, degradation studies (up to 3 months) were performed, providing insight into material stability and degradation profiles relevant for in vitro and in vivo applications.
Third, we assessed the in vitro functional performance of BioChord using a dynamic stretching bioreactor that simulates physiological loading conditions. These experiments demonstrated the scaffold’s ability to support cell attachment and proliferation, confirming its suitability for mechanically active environments.
Finally, a large animal (ovine) study was initiated to evaluate BioChord performance in a clinically relevant in vivo setting. The study focuses on key translational endpoints, including hemocompatibility, inflammatory and fibrotic responses, and the capacity for tissue integration and remodeling under physiological conditions.
Collectively, these activities represent a significant advancement toward the validation of BioChord as a biomimetic, regenerative alternative to current artificial chordae, supporting its progression toward higher technological readiness.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

BioChord is the first bioengineered CT substitute combining a native-like microstructure with regenerative potential, aiming to overcome the long-term limitations associated with conventional chordal repair based on synthetic suture materials. Within this PoC, we performed a comprehensive cross-species characterization of native CTs, generating key structure-function insights that guided the rational biomimetic design of the BioChord platform. These findings, together with preliminary in vitro studies demonstrating progressive cellular infiltration and growth, enabled progression toward functional implantation in a clinically relevant ovine large-animal model, advancing the technology from TRL2 to TRL5. The in vivo studies represent the most important outcome of this PoC project. BioChord demonstrated adequate surgical handling and suture retention, and absence of thrombus formation following implantation (up to 90 days). However, only approximately 25% of the implanted samples maintained complete mechanical integrity after 90 days in vivo, identifying BioChord stability and degradation kinetics as the principal technological limitation of the current platform. Importantly, the identification of this failure mode represents one of the most valuable translational outcomes of the project, providing critical guidance for future optimization strategies. The key needs for future uptake and technological advancement include: i) a more systematic investigation of material degradation profiles under physiologically relevant in vivo conditions, an area currently limited by the reduced predictive capability of existing in vitro degradation models; ii) further optimization of the surgical model/implantation technique to avoid intersection between native and engineered chordae, thereby minimizing abnormal torsional and shear stress components affecting device durability; and iii) additional long-term preclinical studies to optimize biomechanical stability, remodeling behavior, and translational reproducibility. Overall, the project represents the first attempt to engineer functional biomimetic chordae tendineae for regenerative valve repair and, consistently with the high-risk/high-gain ERC philosophy, successfully demonstrated feasibility while identifying critical design parameters necessary to advance the technology toward future clinical translation.