The Relevance of Large Strains in Functional Tissue Engineering of Heart Valves

Abstract

Background: Exposing the developing tissue to flow and pressure in a bioreactor has been shown to enhance tissue formation in tissue-engineered heart valves. Animal studies showed excellent 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 conditioning protocol is an important step towards the use of these valves as aortic heart valve replacements. In this study, the relevance 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 formation with superior mechanical properties over unstrained controls. Overall tissue properties improved with increasing strain levels. Conclusions: The results demonstrate the significance 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

References

• 1 Butler D L, Goldstein S A, Guilak F. Functional tissue engineering: the role of biomechanics.  J Biomech Eng. 2000;  122 570-575
• 2 Hoerstrup S P, Sodian R, Daebritz S. et al . Functional living trileaflet heart valves grown in vitro.  Circulation. 2000;  102 (suppl III) III-44-III-49
• 3 Schnell A M, Hoerstrup S P, Zund G. et al . Optimal cell source for cardiovascular tissue engineering: venous vs. aortic human myofibroblasts.  Thorac Cardiovasc Surg. 2001;  49 221-225
• 4 Hoerstrup S P, Kadner A, Breymann C. et al . Living, autologous pulmonary artery conduits tissue engineered from human umbilical cord cells.  Ann Thorac Surg. 2002;  74 46-52
• 5 Hoerstrup S P, Zund G, Ye Q, Schoeberlein A, Schmid A C, Turina M I. Tissue engineering of a bioprosthetic heart valve: stimulation of extracellular matrix assessed by hydroxyproline assay.  ASAIO J. 1999;  45 397-402
• 6 Hoerstrup S P, Zund G, Schnell A M. et al . Optimized growth conditions for tissue engineering of human cardiovascular structures.  Int J Artif Organs. 2000;  23 817-823
• 7 Breuls R GM, Mol A, Petterson R, Oomens C WJ, Baaijens F PT, Bouten C VC. Monitoring local cell viability in engineered tissues: a fast, quantitative and non-destructive approach.  Tissue Eng. 2003;  9 (2) 269-281 (in press)
• 8 Farndale R W, Buttle D J, Barrett A J. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue.  Biochim Biophys Acta. 1986;  883 173-177
• 9 Kim B S, Nikolovski J, Bonadio J, Mooney D J. Cyclic mechanical strain regulates the development of engineered smooth muscle tissue.  Nat Biotechnol. 1999;  17 979-983
• 10 Kim B S, Mooney D J. Scaffolds for engineering smooth muscle under cyclic mechanical strain conditions.  J Biomech. 2000;  122 210-215
• 11 Stock U A, Vacanti J P. Cardiovascular physiology during fetal development and implications for tissue engineering.  Tissue Eng. 2001;  7 1-7
• 12 Jockenhoevel S, Zund G, Hoerstrup S P, Schnell A, Turina M. Cardiovascular tissue engineering: a new laminar flow chamber for in vitro improvement of mechanical tissue properties.  ASAIO J. 2002;  48 8-11
• 13 Karlon W J, Lee A A, Graham D A, Cruz S D, Ratcliffe A. Fluid shear stress-induced alignment of cultured vascular smooth muscle cells.  J Biomech Eng. 2002;  124 37-43
• 14 Ueba H, Kawakami M, Yaginuma T. Shear stress as an inhibitor of vascular smooth muscle cell proliferation. Role of transforming growth factor-beta1 and tissue-type plasminogen activator.  Arterioscler Thromb Vasc Biol. 1997;  17 1512-1516
• 15 Nackman G B, Fillinger M F, Shafritz R, Wei T, Graham A M. Flow modulates endothelial regulation of smooth muscle cell proliferation: a new model.  Surgery. 1998;  124 353-361
• 16 Weston M W, Yoganathan A P. Biosynthetic activity in heart valve leaflets in response to in vitro flow environments.  Ann Biomed Eng. 2001;  29 752-763
• 17 Driessen N JB, Boerboom R A, Huyghe J M, Bouten C VC, Baaijens F PT. Computational analyses of mechanically induced collagen fibre remodelling in the aortic heart valve. J Biomech Eng 2002 Submitted