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In the Netherlands, there are 250,000 patients with heart failure. Half of these patients die within five years. The best treatment: a donor heart. But: there is a great shortage of these. The Holland Hybrid Heart consortium is therefore working on an alternative: a robot heart, made of soft materials. The research We envision the treatment of patients with heart failure (HF) in such a way that the survival and quality of life of HF patients drastically increases. We aim to achieve this by developing a unique bioinspired total artificial heart that integrates soft robotics and tissue engineering (TE). In the long term, we foresee that this pioneering technology allows us to develop and bring to the clinic a full set of artificial motile organs and tissues that seamlessly integrate with the human body. This will be possible as the novel and exciting technologies underlying the artificial heart developed in this project - soft robotics and in situ TE - can be used to generate a broad range of artificial motile organs such as muscle structures (e.g., limbs), bowels or lungs: The motility and flexibility in shape and size of soft robots make them suitable for mimicking motile organs. Actuators can be embedded within the elastomeric matrix of these robots without compromising their malleable properties. In addition, embodied intelligence provides direct feedback on shape and force, enabling natural behaviour. Biocompatibility of these artificial organs is provided by TE inside the body (in situ) using biodegradable coatings or scaffolds. Such TE scaffolds are cell-free synthetic bio-resorbable implants or linings that can recruit or interact with cells from the bloodstream, leading to gradual replacement of the scaffold by fully endogenous, and thus biocompatible, tissue. Importantly, the cell-free and thus off-the-shelf availability of these scaffolds avoids the high costs and complex logistics inherent to pre-implantation in vitro TE. The Holland Hybrid Heart (HHH) consortium will push the development of these newly emerging technologies forward and combines soft robotics and in situ TE to generate the first biocompatible, soft actuated heart. This project will deliver Proof-of-Principle for full in vivo cardiac functionality of the artificial HHH in large animals. If successful, the HHH will be available for translation to the clinic as an effective treatment for advanced HF in patients and a valid alternative for moderately effective current HF therapies. This is a quantum leap forward in the treatment of HF. Origin A photo in the newspaper inspired Rotterdam heart specialist Jolanda Kluin to develop a robot heart. Kluin immediately contacted the interviewee in the article, Bas Overvelde, head of the Soft Robotic Matter group at Amolf, which develops soft robots. Could he perhaps also make a heart using soft robot techniques? Overvelde believed in it and a collaboration was born. Five years ago, they received a European subsidy of more than 3 million euros. This grant started the previous EU consortium, the EU Hybrid Heart. Last December (2023), Kluin received another 11 million euros from the Dutch government to continue the Holland hybrid heart project. The Holland Hybrid Heart has pivoted to meet the demands of that new grant and now only contains 15 Dutch consortium partners. The consortium is funded by NWA-ORC and the Dutch Heart Foundation. In-kind contributions are also provided by the DCVA, the Dutch Heart Foundation, TrailBlazers, SBMC, EVOS and EE-Labels. The executing academic partners are Erasmus MC, Amolf, TU Eindhoven, University of Twente, TU Delft and Saxion Applied University. This research is driven by patient needs and the Harteraad and Stichting Pulmonale Hypertensie will provide the connections to these patients.

Cardiomyopathies, caused by genetic mutations affecting cardiac muscle components, pose significant economic and societal burdens due to their hereditary nature and early onset. Despite known genetic defects, predicting disease progression remains challenging due to extreme clinical variability. Recent research indicates that cardiomyopathy mutations induce metabolic stress, exacerbated by factors like obesity, which can accelerate disease progression. The Double Dose hypothesis suggests that targeting metabolic stress may offer preventive or curative strategies for these conditions. The Focus The Double Dose Consortium aims to understand how cardiomyopathy-causing mutations lead to structural changes in cardiomyocytes. This interdisciplinary effort combines experts in preclinical research, clinical genetics, health technology assessment, and clinical care focused on cardiomyopathy in both children and adults. The Research The consortium combines experts in preclinical research, clinical genetics, health technology assessment and clinical researchers with a strong clinical focus on cardiomyopathy in children and adults. These experts investigate how obesity and muscle adiposity contribute to vascular and cardiac muscle dysfunction in mutation carriers through the analysis of clinical data, patient samples, and experimental models. They will also study the mechanisms underlying ultrastructural changes in cardiomyocytes caused by these mutations, leading to impaired metabolism, contraction, relaxation defects, and disrupted cellular communication within the heart. Utilizing extensive patient cohorts and ongoing studies, the consortium aims to optimize care for cardiomyopathy patients by assessing the cost-effectiveness of diagnostics and clinical interventions. They plan to translate findings on metabolic alterations into clinical trials targeting treatments that reduce metabolic stress. The Double Dose program will establish biobanks containing serum, tissue, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to provide mechanistic insights into cardiomyopathy pathophysiology and improve diagnosis and care. Origin This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation, together with Stichting Hartedroom. The consortium is a continuation of the Dosis consortium, in which the interaction between mutation and external factors was investigated. They found that cardiomyopathy-mutations induce metabolic stress and that secondary metabolic stress, such as obesity accelerates disease progression.