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J Thorac Cardiovasc Surg 2006;132:737
© 2006 The American Association for Thoracic Surgery
Letter to the Editor |
Institut National de la Santé et de la Recherche Medicale (Inserm) ERI-9, Faculté de Médecine and Clinique de Chirurgie Cardio-vasculaire, Cardiologic Hospital, Lille, France
We thank Drs Stamm and Steinhoff for their comments. In the field of tissue-engineered heart valves, the choice between synthetic and biologic (either allogeneic or xenogenic) scaffolds is a major concern. As have many others, we hypothesized that the best valve replacement remains a heart valve. Porcine heart valves have been used for decades in cardiac surgery with good clinical results, especially in terms of durability in elderly patients. In particular, hemodynamic behavior of the latest generation of porcine bioprostheses, the stentless porcine valves, was found to be similar to that of native aortic valves.
These scaffolds, however, need preimplantation treatment to avoid acute xenogenic rejection. Decellularization seems a promising choice, because it both induces a decrease of cell-induced acute rejection and may allow autologous cell recolonization. Our study suggests that nonenzymatic decellularization may be used without inducing mechanical failure of the matrix in vivo. Previous decellularization procedures, such as deep osmotic shock (with distilled water)1
or use of trypsin and ribonuclease,2 have resulted in graft failure.3 Adverse immune reaction was advocated; however, we observed that a less aggressive decellularization procedure did not induce mechanical failure after 4-month exposure in the systemic arterial strain, suggesting that the decellularization procedure was critical for the in vivo outcome.
Stamm and coworkers4 used an enzymatic decellularization procedure, but they reinforced the scaffold with a biodegradable polymer coating. Short-terms results were satisfactory, but little is known about the long-term behavior of these polymers. Previous long-term studies on biodegradable scaffolds as heart valve substitutes have reported fibrosis, retraction, and graft dysfunction.5
As noted by Stamm and Steinhoff, coagulation and complement activation, with the risk of collagen-induced platelet aggregation early after implantation, are a major concern with decellularized matrices. We found no evidence of thrombus formation on implanted decellularized scaffolds, and thrombosis occurred only in a nondecellularized xenograft. However, it should be underlined that in our study all animals received aspirin therapy (500 mg daily), as in usual clinical practice with biologic valves.
Finally, our study suggests that xenogenic scaffolds decellularized through a nonenzymatic procedure do not induce matrix failure in a sheep model, and interestingly allow partial recellularization in vivo. Longer implantation studies are mandatory to confirm these mechanical results. Moreover, because autologous cell recolonization of these decellularized scaffolds remains only partial, other strategies to induce complete recolonization by proper autologous cells are needed.
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