Translating autologous heart valve tissue engineering from bench to bed.

Tissue engineering is currently being actively investigated to ascertain if it can offer an alternative to prosthetic aortic heart valves that may overcome the current limitations of prosthetic aortic heart valves while at the same time conferring the advantages of a living autologous structure, such as biocompatibility, the capacity to grow, repair, and remodel. In vitro studies have shown tissue-engineered heart valves to have adequate structural and functional properties, indicating a promising future for heart valve tissue engineering. However, criteria are required to be able to evaluate autologous heart valves and to deem them satisfactory for clinical use. Preclinical animal studies are needed, as a precursor to long-term in vivo follow-up studies, to establish such criteria. The first challenge is to find appropriate techniques to evaluate the functionality of tissue-engineered heart valves in vivo without having to kill the animal. As such, the development of such noninvasive techniques that are able to assess the functionality of tissue-engineered heart valves is the next step in translational research. This review discusses methods of evaluating the functionality of autologous heart valves when translating from in vitro to in vivo studies and determines potential assessment criteria imperative to achieve clinical applicability of tissue-engineered heart valves in aortic valve replacement.

[1]  Frederick J. Schoen,et al.  Evolving Concepts of Cardiac Valve Dynamics: The Continuum of Development, Functional Structure, Pathobiology, and Tissue Engineering , 2008, Circulation.

[2]  J.D.F. Habbema,et al.  Prognosis After Aortic Valve Replacement With a Bioprosthesis: Predictions Based on Meta-Analysis and Microsimulation , 2001, Circulation.

[3]  K S Kunzelman,et al.  Re-creation of sinuses is important for sparing the aortic valve: a finite element study. , 2000, The Journal of thoracic and cardiovascular surgery.

[4]  Elliot K Fishman,et al.  Cardiac valve assessment with MR imaging and 64-section multi-detector row CT. , 2006, Radiographics : a review publication of the Radiological Society of North America, Inc.

[5]  Umberto Morbiducci,et al.  Innovative technologies for the assessment of cardiovascular medical devices: state-of-the-art techniques for artificial heart valve testing , 2004, Expert review of medical devices.

[6]  Ralph Weissleder,et al.  Multimodality Molecular Imaging Identifies Proteolytic and Osteogenic Activities in Early Aortic Valve Disease , 2007, Circulation.

[7]  Maarten Merkx,et al.  Fluorescently labeled collagen binding proteins allow specific visualization of collagen in tissues and live cell culture. , 2006, Analytical biochemistry.

[8]  Ralph Weissleder,et al.  Optical Visualization of Cathepsin K Activity in Atherosclerosis With a Novel, Protease-Activatable Fluorescence Sensor , 2007, Circulation.

[9]  A. Bader,et al.  The cardiovascular tissue-reactor: a novel device for the engineering of heart valves. , 2006, Artificial organs.

[10]  Ralph Weissleder,et al.  Detection of Vascular Adhesion Molecule-1 Expression Using a Novel Multimodal Nanoparticle , 2005, Circulation research.

[11]  F. Baaijens,et al.  Collagen fibers reduce stresses and stabilize motion of aortic valve leaflets during systole. , 2004, Journal of biomechanics.

[12]  R. B. Brink Evaluation of prosthetic heart valves by transesophageal echocardiography: problems, pitfalls, and timing of echocardiography. , 2006 .

[13]  P. Libby,et al.  Activated Interstitial Myofibroblasts Express Catabolic Enzymes and Mediate Matrix Remodeling in Myxomatous Heart Valves , 2001, Circulation.

[14]  Ivan Vesely,et al.  Heart Valve Tissue Engineering , 2005 .

[15]  Frederick J Schoen,et al.  Cardiovascular tissue engineering. , 2002, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[16]  Anthony Ratcliffe,et al.  Translation from research to applications. , 2006, Tissue engineering.

[17]  Robert M Nerem,et al.  Unique Morphology and Focal Adhesion Development of Valvular Endothelial Cells in Static and Fluid Flow Environments , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[18]  Axel Pruss,et al.  Decellularized xenogenic heart valves reveal remodeling and growth potential in vivo. , 2006, Tissue engineering.

[19]  F. Guilak,et al.  Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis. , 2006, American journal of physiology. Heart and circulatory physiology.

[20]  M. Cybulsky,et al.  Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. , 1991, Science.

[21]  Frederick J Schoen,et al.  Cardiac valves and valvular pathology: update on function, disease, repair, and replacement. , 2005, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[22]  A. Mehta,et al.  Multiphoton endoscopy: optical design and application to in vivo imaging of mammalian hippocampal neurons , 2003, Conference on Lasers and Electro-Optics, 2003. CLEO '03..

[23]  K. König,et al.  Two-photon microscopes and in vivo multiphoton tomographs--powerful diagnostic tools for tissue engineering and drug delivery. , 2006, Advanced drug delivery reviews.

[24]  B. Vasavada,et al.  Prosthetic heart valves: types and echocardiographic evaluation. , 2007, International journal of cardiology.

[25]  Frederick J. Schoen,et al.  Functional Growth in Tissue-Engineered Living, Vascular Grafts: Follow-Up at 100 Weeks in a Large Animal Model , 2006, Circulation.

[26]  Jan Engvall,et al.  Flow patterns in the aortic root and the aorta studied with time-resolved, 3-dimensional, phase-contrast magnetic resonance imaging: implications for aortic valve-sparing surgery. , 2004, The Journal of thoracic and cardiovascular surgery.

[27]  Frank P T Baaijens,et al.  The role of collagen cross-links in biomechanical behavior of human aortic heart valve leaflets--relevance for tissue engineering. , 2007, Tissue engineering.

[28]  Michael S. Sacks,et al.  Design and Hydrodynamic Evaluation of a Novel Pulsatile Bioreactor for Biologically Active Heart Valves , 2004, Annals of Biomedical Engineering.

[29]  M. Thubrikar,et al.  The mechanism of opening of the aortic valve. , 1979, The Journal of thoracic and cardiovascular surgery.

[30]  W G Henderson,et al.  Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the Veterans Affairs randomized trial. , 2000, Journal of the American College of Cardiology.

[31]  Christopher K Breuer,et al.  Application of tissue-engineering principles toward the development of a semilunar heart valve substitute. , 2004, Tissue engineering.

[32]  Ajit P. Yoganathan,et al.  An Ex Vivo Study of the Biological Properties of Porcine Aortic Valves in Response to Circumferential Cyclic Stretch , 2006, Annals of Biomedical Engineering.

[33]  Ralph Weissleder,et al.  Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis , 2006, Circulation.

[34]  D J Wheatley,et al.  Twelve-year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses. , 1991, The New England journal of medicine.

[35]  A. Yoganathan,et al.  Comparative hydrodynamic evaluation of bioprosthetic heart valves. , 2001, The Journal of heart valve disease.

[36]  S. Hoerstrup,et al.  In vitro heart valve tissue engineering. , 2007, Methods in molecular medicine.

[37]  E. Steyerberg,et al.  Human Tissue Valves in Aortic Position: Determinants of Reoperation and Valve Regurgitation , 2001, Circulation.

[38]  Y Imai,et al.  Regulation of the aortic valve opening. In vivo dynamic measurement of aortic valve orifice area. , 1995, The Journal of thoracic and cardiovascular surgery.

[39]  S. Hoerstrup,et al.  Engineering of biologically active living heart valve leaflets using human umbilical cord-derived progenitor cells. , 2006, Tissue engineering.

[40]  S. Hoerstrup,et al.  Umbilical cord blood derived endothelial progenitor cells for tissue engineering of vascular grafts. , 2004, The Annals of thoracic surgery.

[41]  KAREN MENDELSON,et al.  Heart Valve Tissue Engineering: Concepts, Approaches, Progress, and Challenges , 2006, Annals of Biomedical Engineering.

[42]  I Vesely,et al.  The role of elastin in aortic valve mechanics. , 1997, Journal of biomechanics.

[43]  Marcel C M Rutten,et al.  Autologous Human Tissue-Engineered Heart Valves: Prospects for Systemic Application , 2006, Circulation.

[44]  Dwight E. Harken,et al.  Aortic valve replacement with a gaged ball valve , 1962 .

[45]  M. Yacoub,et al.  Human mesenchymal stem cells induce T cell anergy and downregulate T cell allo-responses via the TH2 pathway: relevance to tissue engineering human heart valves. , 2006, Tissue engineering.

[46]  T. Shinoka Tissue engineered heart valves: autologous cell seeding on biodegradable polymer scaffold. , 2002, Artificial organs.

[47]  Frederick J. SchoenT Review Article Cardiac valves and valvular pathology B Update on function, disease, repair, and replacement , 2005 .

[48]  Artur Lichtenberg,et al.  Preclinical Testing of Tissue-Engineered Heart Valves Re-Endothelialized Under Simulated Physiological Conditions , 2006, Circulation.

[49]  Magdi H. Yacoub,et al.  Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch. , 2006, Cardiovascular research.

[50]  Michael Markl,et al.  Time-resolved three-dimensional magnetic resonance velocity mapping of aortic flow in healthy volunteers and patients after valve-sparing aortic root replacement. , 2005, The Journal of thoracic and cardiovascular surgery.

[51]  J. Lindner,et al.  Molecular Imaging of Inflammation in Atherosclerosis With Targeted Ultrasound Detection of Vascular Cell Adhesion Molecule-1 , 2007, Circulation.

[52]  M. Yacoub,et al.  Potential for synthesis and degradation of extracellular matrix proteins by valve interstitial cells seeded onto collagen scaffolds. , 2006, Tissue engineering.

[53]  Frederick J Schoen,et al.  Evolution of cell phenotype and extracellular matrix in tissue-engineered heart valves during in-vitro maturation and in-vivo remodeling. , 2002, The Journal of heart valve disease.

[54]  A. Yoganathan,et al.  Heart valve function: a biomechanical perspective , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[55]  Marcel C. M. Rutten,et al.  Tissue Engineering of Human Heart Valve Leaflets: A Novel Bioreactor for a Strain-Based Conditioning Approach , 2005, Annals of Biomedical Engineering.

[56]  Andrew L Rivard,et al.  The current state of in-vivo pre-clinical animal models for heart valve evaluation. , 2005, The Journal of heart valve disease.

[57]  Zhaoming He,et al.  Cyclic Pressure Affects the Biological Properties of Porcine Aortic Valve Leaflets in a Magnitude and Frequency Dependent Manner , 2004, Annals of Biomedical Engineering.

[58]  Maarten Merkx,et al.  High resolution imaging of collagen organisation and synthesis using a versatile collagen specific probe. , 2007, Journal of structural biology.

[59]  Borut Marincek,et al.  Electrocardiographically gated multi-detector row CT for assessment of valvular morphology and calcification in aortic stenosis. , 2002, Radiology.

[60]  Artur Lichtenberg,et al.  Flow-dependent re-endothelialization of tissue-engineered heart valves. , 2006, The Journal of heart valve disease.

[61]  Michael S Sacks,et al.  From Stem Cells to Viable Autologous Semilunar Heart Valve , 2005, Circulation.

[62]  C. Mavroudis,et al.  The Ross operation in children: effects of aortic annuloplasty. , 2007, The Annals of thoracic surgery.

[63]  Vasilis Ntziachristos,et al.  Inflammation in Atherosclerosis: Visualizing Matrix Metalloproteinase Action in Macrophages In Vivo , 2006, Circulation.

[64]  W. Webb,et al.  Nonlinear magic: multiphoton microscopy in the biosciences , 2003, Nature Biotechnology.

[65]  Michael S Sacks,et al.  Cyclic flexure and laminar flow synergistically accelerate mesenchymal stem cell-mediated engineered tissue formation: Implications for engineered heart valve tissues. , 2006, Biomaterials.

[66]  R. Hopkins Tissue engineering of heart valves: decellularized valve scaffolds. , 2005, Circulation.

[67]  C K Breuer,et al.  Tissue engineering heart valves: valve leaflet replacement study in a lamb model. , 1995, The Annals of thoracic surgery.

[68]  M. Eijkemans,et al.  Serial echocardiographic assessment of neo-aortic regurgitation and root dimensions after the modified Ross procedure. , 2006, The Journal of heart valve disease.

[69]  F. Schoen,et al.  Human Semilunar Cardiac Valve Remodeling by Activated Cells From Fetus to Adult: Implications for Postnatal Adaptation, Pathology, and Tissue Engineering , 2006, Circulation.

[70]  K. König,et al.  Multiphoton autofluorescence imaging of intratissue elastic fibers. , 2005, Biomaterials.

[71]  M. Alley,et al.  Time-Resolved 3-Dimensional Velocity Mapping in the Thoracic Aorta: Visualization of 3-Directional Blood Flow Patterns in Healthy Volunteers and Patients , 2004, Journal of computer assisted tomography.