In situ tissue engineering using a biodegradable synthetic scaffold that recruits endogenous cells from the bloodstream is emerging as a promising technology to create living heart valves inside the human body having the potential to last a life-time: one valve for life. Compared to classical tissue engineered heart valves this new technology demonstrates off-the-shelf availability at substantially reduced cost. The current proposal aims to further develop the synthetic biomaterials needed for the in situ tissue engineering of heart valves, to process these materials into a functional heart valve scaffold, and to perform all the necessary pre-clinical experiments to enable first-in-man clinical application. A novel approach to the biodegradable scaffold will be developed, that combines a relatively slowly degrading (months) elastomeric material with a fast degrading (weeks) bioactive hydrogel material. These materials will be processed into a fibrous heart valve scaffold by means of electrospinning. The elastomeric material ensure long term functionality of the valve while supporting in-vivo mature tissue formation, while the fast eroding hydrogel material controls the early inflammatory response and creates the necessary void space between the elastomeric fibers. A minimally invasive, transapical, implantation technique will be used for the placement of the heart valve scaffold at the aortic position, following our recent results. For this purpose, tailor-made stents will be developed.