Introduction In the emerging field of tissue engineering, organ replacements are fabricated on the basis of a biodegradable carrier – the scaf- fold – seeded with the patient’s own cells. The carrier, which can either consist of a biologically derived material or a synthetic polymer, provides the developing tissue with sufficient mechan- ical properties during the in vitro culturing period. Despite the success of this approach, problems arose concerning the me- chanical properties of engineered tissues that serve a predomi- nantly biomechanical function, such as heart valves. Increasing evidence suggests mechanical conditioning as a valuable method to increase the mechanical properties of engineered tissues prior to implantation [1]. Tissue-engineered heart valves cultured in a bioreactor with mechanical stimulation have shown functional- ity for prolonged periods of time when placed in the pulmonary position in animal models [2]. Still, these heart valve replace- ments appear to lack mechanical strength to withstand stresses arising at the aortic position. Optimizing the in vitro mechanical conditioning protocol might help solving this problem. The Relevance of Large Strains in Functional Tissue Engineering of Heart Valves A.Mol 1,2 C.V.C.Bouten 2 G.Zünd 1 C.I.Günter 1 J.F.Visjager 3 M.I.Turina 1 F.P.T.Baaijens 2 S.P.Hoerstrup 1 Affiliation 1 Clinic for Cardiovascular Surgery, University Hospital Zurich, Switzerland 2 Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands 3 Institute for Polymers, Swiss Federal Institute of Technology, Zurich, Switzerland Dedication Presented at the 32 nd annual meeting of The German Society for Thoracic and Cardiovascular Surgery in Leipzig, February 23 – 26, 2003 Correspondence MD Simon Philipp Hoerstrup · Clinic for Cardiovascular Surgery, University Hospital Zürich · Raemistrasse 100 · 8091 Zurich · Switzerland · Phone: +41/1/2553801 · Fax: +41/1/2554369 · E-mail: simon_philipp.hoerstrup@chi.usz.ch Received: February 27, 2003 Bibliography Thorac Cardiov Surg 2003; 51: 78–83 · # Georg Thieme Verlag Stuttgart · New York · ISSN 0171-6425 Abstract Background: Exposing the developing tissue to flow and pres- sure in a bioreactor has been shown to enhance tissue formation in tissue-engineered heart valves. Animal studies showed excel- lent functionality in these valves in the pulmonary position. However, they lack the mechanical strength for implantation in the high-pressure aortic position. Improving the in vitro condi- tioning protocol is an important step towards the use of these valves as aortic heart valve replacements. In this study, the rele- vance of large strains to improve the mechanical conditioning protocol was investigated. Methods: Using a newly developed device, engineered heart valve tissue was exposed to increasing cyclic strain in vitro. Tissue formation and mechanical properties were analyzed and compared to unstrained controls. Results: Straining resulted in more pronounced and organized tissue for- mation with superior mechanical properties over unstrained controls. Overall tissue properties improved with increasing strain levels. Conclusions: The results demonstrate the signifi- cance of large strains in promoting tissue formation. This study may provide a methodological basis for tissue engineering of heart valves appropriate for systemic pressure applications. Key words Tissue engineering · heart valves · mechanical stress Original Cardiovascular 78