Ann Thorac Surg 2005;79:896
© 2005 The Society of Thoracic Surgeons
INVITED COMMENTARY
Paul Simon, MD,
Marie-Theres Kasimir, MD,
Erwin Rieder, MD,
Guenter Weigel, MD
Department of Cardiac and Thoracic Surgery,Medical University of Vienna,Waehringer Guertel 18-20,Vienna, A-1090 Austria
(E-mail: paul.simon{at}univie.ac.at).
This study describes another important attempt to overcome the limitations of currently available biomaterials in cardiac surgery. Decellularization of biomaterials, in this case ovine pulmonary patches, is thought to reduce antigenicity. However the efficiency of various protocols may differ importantly. In this study a combined anionic–enzymatic protocol is used and cells were effectively removed. Three groups of vascular patches, cryopreserved, cryopreserved–decellularized, and decellularized were implanted as vascular patches in the descending aorta and pulmonary artery in juvenile sheep for 10 and 20 weeks. The patches were well incorporated and no failures or calcification were observed. The antigenicity of decellularized samples appeared to be minimal as indicated by the absence of panel reactive antibodies. Cells repopulated the decellularized tissue samples in a time-dependent fashion and the staining for smooth-muscle actin suggested that these were myofibroblasts.
Several questions remain. The sheep was used as the standard model for the evaluation of heart valves, but it may not be the ideal model to transfer results to humans. Sheep have a tendency to endothelialize almost any material, whether biological or artificial. This is in sharp contrast to humans who seem to lack this ability. In fact, we have seen no cell repopulation of a decellularized heart valve implanted in humans up to 1.5 years. Furthermore, in this sheep model the cryopreserved samples behaved very differently from decellularized samples whether cryopreserved or not. It is well known that homografts become acellular after implantation, which in the case of this study corresponds to the cryopreserved allografts. What makes this acellular matrix so different from the decellularized material that it does not even become repopulated in sheep? Or in other words, what makes the decellularized matrix conducive to repopulation? The authors describe "fibrous sheathing of the tissues on the inside and more pronounced on the outside as part of the healing process" and suggest that this is important for the repopulation of the matrix. However, dense fibrous sheathing was an important failure mode leading to severe obstruction seen in the man implants with a decellularized heart valve.
As the pressure is mounting to develop superior biomaterials, especially in pediatric cardiac surgery where the need is particularly felt, we must remain cautious because experimental results may not be readily transferred to humans. The decellularized tissue may not be as biologically inert as is frequently suggested by removing the cells, but it may still elicit an inflammatory response.
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Ann. Thorac. Surg. 2005 79: 888-896.
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