Abstract
Homograft availability and durability remain big challenges. Increasing the post-mortem ischaemic harvesting time beyond 24 h increases the potential donor pool. Cryopreservation, routinely used to preserve homografts, damages the extracellular matrix (ECM), contributing to valve degeneration. Decellularization might preserve the ECM, promoting host-cell infiltration and contributing towards better clinical outcomes. This study compared the performance of cryopreserved versus decellularized pulmonary homografts in the right ventricle outflow tract (RVOT) of a juvenile ovine model. Homografts (n = 10) were harvested from juvenile sheep, subjected to 48 h post-mortem cold ischaemia, cryopreserved or decellularized and implanted in the RVOT of juvenile sheep for 180 days. Valve performance was monitored echocardiographically. Explanted leaflet and wall tissue evaluated histologically, on electron microscopical appearance, mechanical properties and calcium content. In both groups the annulus diameter increased. Cryopreserved homografts developed significant (¾) pulmonary regurgitation, with trivial regurgitation (¼) in the decellularized group. Macroscopically, explanted cryopreserved valve leaflets retracted and thickened while decellularized leaflets remained thin and pliable with good coaptation. Cryopreserved leaflets and walls demonstrated loss of interstitial cells with collapsed collagen, and decellularized scaffolds extensive, uniform ingrowth of host-cells with an intact collagen network. Calcific deposits were shown only in leaflets and walls of cryopreserved explants. Young fibroblasts, with vacuoles and rough endoplasmic reticulum in the cytoplasm, repopulated the leaflets and walls of decellularized scaffolds. Young’s modulus of wall tissue in both groups increased significantly. Cryopreserved valves deteriorate over time due to loss of cellularity and calcification, while decellularized scaffolds demonstrated host-cell repopulation, structural maintenance, tissue remodelling and growth potential.
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Acknowledgements
We would like to thank Miss H Grobler from the Centre for Electron Microscopy for all the tissue preparation for SEM and TEM, the UFS Animal Research Centre for their assistance, Department of Anaesthesiology and all perfusion technologists.
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The study was funded by the Department of Cardiothoracic Surgery, University of the Free State, Bloemfontein, South Africa.
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van den Heever, J.J., Jordaan, C.J., Lewies, A. et al. Comparison of the function and structural integrity of cryopreserved pulmonary homografts versus decellularized pulmonary homografts after 180 days implantation in the juvenile ovine model. Cell Tissue Bank 23, 347–366 (2022). https://doi.org/10.1007/s10561-021-09948-2
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DOI: https://doi.org/10.1007/s10561-021-09948-2