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DOI: 10.1055/s-2008-1037922
Enhanced tissue development in autologous tissue-engineered heart valves using a customised bioreactor conditioning system
Our group has previously demonstrated the synthesis of completely autologous fibrin-based heart valves using the principles of tissue engineering. The present approach aims to guide more mature tissue development in fibrin-based valves based on in vitro conditioning in a customised bioreactor system.
Valve structures were cast using fibrin suspensions (n=8) and ovine carotid artery myofibroblasts (10×106 cells/ml) in a mould, before being subjected to 12 days of conditioning in a bioreactor. The pulse rate was increased from 5 to 10 b.p.m. after 6 days, while a pressure difference of 20mm H2O was maintained over the valve leaflets. Control valves were cultured under stirred conditions. Cell phenotype and extracellular matrix (ECM) composition were analysed in all samples and compared to native valve tissue.
Conditioned valve leaflets showed reduced tissue shrinkage compared to controls. Limited ECM synthesis was evident in stirred controls, while the majority of cells were detached from the fibrin. Dynamic conditioning increased cell attachment/alignment and expression of α-SMA, while enhancing the deposition of ECM proteins, particularly types I and III collagen. There was no evidence for elastin synthesis in either control or conditioned samples.
The present study demonstrates that the application of low pressure conditions and increasing pulsatile flow not only enhances seeded cell attachment and alignment within fibrin-based heart valves, but dramatically changes the manner in which these cells generate ECM proteins and remodel the valve matrix. Optimised dynamic conditioning, therefore, might enhance the tissue properties of fibrin-based valves sufficiently to allow surgical implantation.