Trockenkonservierung dezellularisierter Herzklappen für die kardiale Regenerationsmedizin
Dry preservation of decellularized heart valves for cardiac regenerative medicine
Projektverantwortliche: Prof. Dr. Ir. Willem F. Wolkers
Laufzeit: Februar 2020 bis Januar 2022
Drittmittelprojekt: Hirsch foundation, 50.000 EUR
Reproduktionsmedizinische Einheit der Kliniken
Decellularized heart valve tissues can be used to replace a malfunctioning heart valve. This option is particularly suitable for young patients, because decellularized tissues have regeneration potential. We have pioneered in developing methods for dry preservation of mammalian cells and tissues and demonstrated that this can be done using disaccharides such as sucrose or trehalose which can be found at high concentrations in anhydrobiotic organisms that naturally survive drying. Drying of decellularized heart valves may alter the properties of the extracellular matrix and impair their in vivo efficacy. The central aim of this project is to test if sucrose can be used for dry preservation of heart valves so that they can be safely used for transplantation. We already established methods to freeze-dry heart valves, but their storage stability needs to be demonstrated. In this project we plan to evaluate if vacuum-drying, which lacks a damaging freezing step, can be used as an alternative drying method. The second objective is to study the effects of (freeze-)drying on scaffold structure, and matrix biomolecules directly after drying as well during storage under normal (4°C or room temperate) and accelerated aging (37°C/high relative humidity) storage conditions. The general tissue architecture will be studied on hematoxylin-eosin stained tissue sections, whereas Fourier transform infrared spectroscopy (FTIR) will be used to obtain spectral fingerprints of tissues during storage. For the latter principal component analysis of the spectra will be used to evaluate tissue modifications during storage. Furthermore, accumulation of oxidative damage will be determined. We postulate that overall tissue structural appearance, and therewith functionality, are compromised by ice crystals, and that this can be minimized by reducing the tissue water content prior to freezing, or to avoid ice formation by using vacuum drying.