Modified tissue cardiomyoplasty and tissue engineered heart valves for congenital heart disease surgery
Final Report Abstract
The goal of this project was the generation of bioartificial contractile myocardial tissue, which can be used in combination with a tissue engineered heart valve to reconstruct the right ventricular outflow tract (RVOT) in impaired hearts. The “proof of principle” constructions, autologous vascularized matrix (AutoVaM) in combination with TE pulmonary valves, revealed a better out come in treated minipigs then the use of pericardium which is currently used in the clinical situation to form heart replacement tissue. So this method might be a real alternative to the standard procedure conducted in pediatric surgery. Bioartificial cardiac tissue can be generated on the basis of neonatal rat cardiac cells cultivated in a matrigel/collagen matrix in combination with SIS as a carrier matrix and this tissue can be maturated by mechanical stimulation. The replacement of the matrix as of matrigel/collagen with SIS-gel and the replacement of the rat cell with meanwhile available human cells as cardiomyocytes, fibroblasts and endothelial cells differentiated from iPS cells will facilitate a functional approach in a large animal model as immunosuppressed minipig or baboon. Even though the repopulation of the vessel bed in BioVaM was successfully achieved with RHE cells as well as with human umbilical cord blood EPC derived ECs and HUVECs, primary pig endothelial cells from various origin were not able to withstand residual detergent remnants. Since the inner lining of the vessel bed with endothelial cells is crucial to prevent thrombosis in the perfused matrix and therefore in the cardiac construct, major efforts must be taken to elaborate a decellularization protocol that allows the survival and propagation of an endothelium in the decellularized structure. This to further enhance the advantages of TE tissue used for RVOT reconstruction. In conclusion, with this present study we generated experimental evidence that RVOT reconstruction with TE materials might be beneficial in comparison to standard operational techniques.
Publications
- Engineering a novel three-dimensional contractile myocardial patch with cell sheets and decellularised matrix. Eur J Cardiothorac Surg. 2010 Oct;38(4):450-5
Hata H, Bär A, Dorfman S, Vukadinovic Z, Sawa Y, Haverich A, Hilfiker A
