Growth and remodeling play opposing roles during postnatal human heart valve development

Tissue growth and remodeling are known to govern mechanical homeostasis in biological tissue, but their relative contributions to homeostasis remain unclear. Here, we use mechanical models, fueled by experimental findings, to demonstrate that growth and remodeling have different effects on heart valve stretch homeostasis during physiological postnatal development. Two developmental stages were considered: early-stage (from infant to adolescent) and late-stage (from adolescent to adult) development. Our models indicated that growth and remodeling play opposing roles in preserving tissue stretch and with time. During early-stage development, excessive tissue stretch was decreased by tissue growth and increased by remodeling. In contrast, during late-stage development tissue stretch was decreased by remodeling and increased by growth. Our findings contribute to an improved understanding of native heart valve adaptation throughout life, and are highly relevant for the development of tissue-engineered heart valves.

[1]  Sandra L. Johnson,et al.  Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs , 2016, Nature Communications.

[2]  V. Mironov,et al.  Age-related analysis of structural, biochemical and mechanical properties of the porcine mitral heart valve leaflets , 2013, Connective tissue research.

[3]  Suzanne Sullivan,et al.  Active Adaptation of the Tethered Mitral Valve: Insights Into a Compensatory Mechanism for Functional Mitral Regurgitation , 2009, Circulation.

[4]  Y. Ostchega,et al.  Mean systolic and diastolic blood pressure in adults aged 18 and over in the United States, 2001-2008. , 2011, National health statistics reports.

[5]  F. Schoen.  Mechanisms of function and disease of natural and replacement heart valves. , 2012, Annual review of pathology.

[6]  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.

[7]  C. Oomens,et al.  Computational model predicts cell orientation in response to a range of mechanical stimuli , 2014, Biomechanics and modeling in mechanobiology.

[8]  M. Kural,et al.  Mechanoregulation of valvular interstitial cell phenotype in the third dimension. , 2014, Biomaterials.

[9]  J D Humphrey,et al.  Stress-modulated growth, residual stress, and vascular heterogeneity. , 2001, Journal of biomechanical engineering.

[10]  Ellen Kuhl,et al.  On the effect of prestrain and residual stress in thin biological membranes. , 2013, Journal of the mechanics and physics of solids.

[11]  Isabel Rey Madeira,et al.  The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. , 2004, Pediatrics.

[12]  R A Levine,et al.  Insights from three-dimensional echocardiography into the mechanism of functional mitral regurgitation: direct in vivo demonstration of altered leaflet tethering geometry. , 1997, Circulation.

[13]  Benedikt Weber,et al.  Transcatheter implantation of homologous "off-the-shelf" tissue-engineered heart valves with self-repair capacity: long-term functionality and rapid in vivo remodeling in sheep. , 2014, Journal of the American College of Cardiology.

[14]  Chris B Schaffer,et al.  Cyclic strain anisotropy regulates valvular interstitial cell phenotype and tissue remodeling in three-dimensional culture. , 2012, Acta biomaterialia.

[15]  Jolanda Kluin,et al.  In situ heart valve tissue engineering using a bioresorbable elastomeric implant - From material design to 12 months follow-up in sheep. , 2017, Biomaterials.

[16]  Jay D. Humphrey,et al.  Mechanotransduction and extracellular matrix homeostasis , 2014, Nature Reviews Molecular Cell Biology.

[17]  F P T Baaijens,et al.  Age-dependent changes of stress and strain in the human heart valve and their relation with collagen remodeling. , 2016, Acta biomaterialia.

[18]  Jay D. Humphrey,et al.  A CONSTRAINED MIXTURE MODEL FOR GROWTH AND REMODELING OF SOFT TISSUES , 2002 .

[19]  J D Humphrey,et al.  Perspectives on biological growth and remodeling. , 2011, Journal of the mechanics and physics of solids.

[20]  A. Ascenzi.  Biomechanics and Galileo Galilei. , 1993, Journal of biomechanics.

[21]  Christopher A. Durst,et al.  Age-related changes in material behavior of porcine mitral and aortic valves and correlation to matrix composition. , 2010, Tissue engineering. Part A.

[22]  Anita Driessen-Mol,et al.  Age-Dependent Changes in Geometry, Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves , 2016, PloS one.

[23]  Frank P T Baaijens,et al.  Mechanical characterization of anisotropic planar biological soft tissues using large indentation: a computational feasibility study. , 2005, Journal of biomechanical engineering.

[24]  B. Rosner,et al.  The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents , 2004 .

[25]  Frank P T Baaijens,et al.  Mechanical characterization of anisotropic planar biological soft tissues using finite indentation: experimental feasibility. , 2008, Journal of biomechanics.

[26]  Y. C. Fung,et al.  Biomechanical Aspects of Growth and Tissue Engineering , 1990 .

[27]  Sandra Loerakker,et al.  A computational analysis of cell-mediated compaction and collagen remodeling in tissue-engineered heart valves , 2016 .

[28]  Vladimir Kasyanov,et al.  Comparison of biomechanical and structural properties between human aortic and pulmonary valve. , 2004, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[29]  A F Bolger,et al.  Papillary muscle-left ventricular wall "complex". , 1997, The Journal of thoracic and cardiovascular surgery.

[30]  B. Griffin,et al.  Apparently normal mitral valves in patients with heart failure demonstrate biochemical and structural derangements: an extracellular matrix and echocardiographic study. , 2005, Journal of the American College of Cardiology.

[31]  Ellen Kuhl,et al.  Evidence of adaptive mitral leaflet growth. , 2012, Journal of the mechanical behavior of biomedical materials.

[32]  Robert A Levine,et al.  Mitral Leaflet Adaptation to Ventricular Remodeling: Occurrence and Adequacy in Patients With Functional Mitral Regurgitation , 2008, Circulation.

[33]  Frank P T Baaijens,et al.  Modeling the mechanics of tissue-engineered human heart valve leaflets. , 2007, Journal of biomechanics.

[34]  Suzanne Sullivan,et al.  Mitral Leaflet Adaptation to Ventricular Remodeling: Prospective Changes in a Model of Ischemic Mitral Regurgitation , 2009, Circulation.

[35]  J D Humphrey,et al.  Fundamental role of axial stress in compensatory adaptations by arteries. , 2009, Journal of biomechanics.

[36]  F P T Baaijens,et al.  Effects of valve geometry and tissue anisotropy on the radial stretch and coaptation area of tissue-engineered heart valves. , 2013, Journal of biomechanics.

[37]  Ankush Aggarwal,et al.  In-vivo heterogeneous functional and residual strains in human aortic valve leaflets. , 2016, Journal of biomechanics.

[38]  A. Angrist,et al.  Age-related collagen and elastin content of human heart valves. , 1967, Journal of gerontology.

[39]  John J Spinelli,et al.  The challenge of defining normality for human mitral and aortic valves: geometrical and compositional analysis. , 2002, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[40]  Theo Arts,et al.  Computational modeling of volumetric soft tissue growth: application to the cardiac left ventricle , 2009, Biomechanics and modeling in mechanobiology.

[41]  Michael S Sacks,et al.  In vivo monitoring of function of autologous engineered pulmonary valve. , 2010, The Journal of thoracic and cardiovascular surgery.

[42]  Brenton D. Hoffman,et al.  Dynamic molecular processes mediate cellular mechanotransduction , 2011, Nature.

[43]  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.

[44]  C J Cyron,et al.  Vascular homeostasis and the concept of mechanobiological stability. , 2014, International journal of engineering science.

[45]  F. Baaijens,et al.  A thermodynamically motivated model for stress-fiber reorganization , 2016, Biomechanics and modeling in mechanobiology.

[46]  Joe McCarthy,et al.  An integrated approach , 2001 .

[47]  R. Ogden,et al.  Hyperelastic modelling of arterial layers with distributed collagen fibre orientations , 2006, Journal of The Royal Society Interface.

[48]  Christopher J. Ploch,et al.  Author ' s personal copy Growing skin : A computational model for skin expansion in reconstructive surgery , 2011 .

[49]  Serdar Göktepe,et al.  A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis. , 2010, Journal of theoretical biology.

[50]  Frederick J Schoen,et al.  Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves. , 2004, The Journal of heart valve disease.

[51]  A. McCulloch,et al.  Stress-dependent finite growth in soft elastic tissues. , 1994, Journal of biomechanics.

[52]  J. Humphrey.  Vascular Adaptation and Mechanical Homeostasis at Tissue, Cellular, and Sub-cellular Levels , 2007, Cell Biochemistry and Biophysics.

[53]  Thomas Schmitz-Rode,et al.  In vivo remodeling and structural characterization of fibrin-based tissue-engineered heart valves in the adult sheep model. , 2009, Tissue engineering. Part A.

[54]  Frank P. T. Baaijens,et al.  Remodelling of the angular collagen fiber distribution in cardiovascular tissues , 2007, Biomechanics and modeling in mechanobiology.

[55]  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.

[56]  Ellen Kuhl,et al.  Growing matter: a review of growth in living systems. , 2014, Journal of the mechanical behavior of biomedical materials.

[57]  J D Humphrey,et al.  Complementary vasoactivity and matrix remodelling in arterial adaptations to altered flow and pressure , 2009, Journal of The Royal Society Interface.