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BioChord: biomimetic engineered chordae tendineae for valve repair and regeneration
Project title: BioChord – Biomimetic engineered chordae tendineae for valve repair and regeneration
Start/end date: 1 October 2023 – 31 March 2026
Funding Agency/Programme: European Research Council (ERC) – Proof Of Concept (ERC-2023-POC)
Partnership: Fondazione Ri.MED
Abstract: The human heart is among those organs suffering from a limited capacity to self-regenerate. Heart diseases continue to be a leading cause of mortality with suboptimal therapeutic options. Thus, deploying new therapeutic strategies for tissue repair is a primary objective in modern cardiac medicine. Valvular heart diseases, such as those related to the Mitral Valve (MV), are the leading causes of cardiovascular morbidity and mortality worldwide, affecting 5.1% of the 65+ years old population. In particular, MV regurgitation, one of the most common valvopathies, affects over 24 million people worldwide. Since the fundamental nature of MV regurgitation is mechanical, caused by physical, irreversible damage to the restraining force structures of the valvular apparatus, the only effective treatment is limited to the surgical approaches that include MV repair or replacement. However, when the regurgitation is due to Chordae Tendinae (CT) elongation or rupture, several studies have demonstrated the substantial advantages of MV repair, using a substitute for the damaged CT vs. MV replacement. Currently, the expanded polytetrafluoroethylene (ePTFE) has become the standard approach in CT repair/replacement. However, several complications (rupture, calcification, detachment, fibrosis, and slippage) have been observed. Hence, there continues to be an urgent need to develop better MV repair techniques that are simple, effective, and durable. In this proposal, we intend to further advance and validate BioChord, the first ever polymeric bioengineered regenerative CT, designed to first repair the MV by replacing the diseased CT, providing mechanical support to the valvular apparatus, then to be restored by the patient tissue, progressively becoming a functional tendon like structure that, as a native CT, while connecting the valve leaflet to the papillary muscle, will sustain the valvular apparatus with blood and nutrients.
Principal Investigator: Antonio D’Amore
HemoStratum – Development of a bioengineered basement membrane to enhance the performance of blood-contacting devices
Start date/end date: April 2026 – September 2027
Funding Agency/Programme: European Research Council (ERC) – Proof Of Concept (ERC-2025-POC)
Partnership: Fondazione Ri.MED
Abstract: Each year, over 10 million transitory and permanent blood-contacting devices are implanted worldwide, playing a crucial role in addressing cardiovascular diseases and providing life-sustaining support. However, despite their widespread use, sub-optimal biocompatibility still represents a major challenge, compromising safety, efficacy, and durability. Up to 70% of patients experience device-related hemocompatibility issues, significantly affecting their quality of life. To mitigate these risks, antithrombotic drugs are commonly prescribed, yet these systemic treatments come with severe complications, including postoperative bleeding, stroke, and hemorrhage. To address these limitations, material surface modification strategies have been explored to improve the hemocompatibility of blood-contacting devices, with a particular emphasis on promoting stable endothelialization. Among these approaches, physical modifications, such as surface patterning, are considered superior to biological and chemical functionalization because they offer a long-lasting performance, without degrading or losing functionality over time, unlike conventional surface coatings. Despite the continued interest from both industrial and academic research, there are no clinically available bioengineered substrates that integrate mesoscale and microscale surface features able to promote and maintain stable device endothelialization that can ensure long-term resistance to thrombus formation. In this proposal, we aim to develop HemoStratum, a bioengineered substrate fabricated by our proprietary processing technology. By integrating electrodeposition and photolithography, HemoStratum leverage on both microfibers and meso-patterns identified to promote endothelial cell proliferation and structural organization. This notion represents a radical innovation that can enhance hemocompatibility of a broad spectrum of blood-contacting devices while ensuring long-term stability, and durability.
Principal Investigator: Antonio D’Amore