Objectives & impact
The key objective of ImaValve is to provide a minimally invasive solution to create living, durable heart valves using an in situ tissue engineering approach. To this end, a scaffold will be designed that can be implanted using a minimally invasive transcatheter technique. After implantation, the scaffold will aid tissue formation while the material is slowly resorbed by the body, allowing the scaffold to gradually transform into a living valve that lasts a lifetime. Within the biodegradable scaffold, a slow degrading (months-years) elastomeric material is combined with a fast eroding (weeks) bioactive hydrogel material. The elastomeric material is required to fulfil challenging mechanical loading and durability demands that ensure long-term functionality of the valve, while supporting homeostatic tissue formation and maturation in-vivo. The hydrogel material is introduced to guide the early inflammatory response to the biomaterial via incorporation of bioactive moieties using a supramolecular ‘mix-and-match’ approach. Next to the bioactive role, the hydrogel material will also create the necessary void space between the electrospun fibers to enable colonization of the scaffold with blood circulating cells. These materials will be processed via an electrospinning technique into a functional heart valve scaffold. The resulting electrospun scaffolds will be extensively tested for function and durability prior to implantation of the fibrous heart valve scaffold in large animals. First, the stent loading and delivery system will be optimized at pulmonary position, where hemodynamic loads are lower, to increase the success rate of the minimally invasive aortic placement procedure in large animals. Short-, mid- and long- term functional and morphological follow up of the implanted heart valves will be performed, in order to achieve benchmarks and guidelines for first-in-man clinical trial.
Congenital heart disease represents a potentially life threatening situation and treatment by highly invasive surgical interventions with substantial morbidity and mortality is often necessary. To date there is no clinically satisfactory treatment modality available for heart valve defects. Current commercially available prosthetic heart valves are non-viable structures that cannot grow, repair or adapt to functional demand changes. In this respect, young recipients of prosthetic heart valves have reduced life expectancy compared to age-matched healthy individuals and may encounter serious valve-related morbidity throughout life.
ImaValve improves the quality of life of heart valve patients by creating a biodegradable heart valve construct that gradually transforms into a living valve at the site of implantation, growing and remodelling for the patient’s life-time. These living valves avoid the need for numerous reoperations in young and adult recipients, and omits the necessity for chronic anticoagulation therapy. Moreover, this approach enables a minimally invasive implantation procedure of heart valve substitutes in patients younger than 65 years of age. The superior performance of these living valves compared to non-living substitutes could significantly enhance the quality of life and life perspective of future heart valve recipients.