title: Age-dependent changes of stress and strain in the human heart valve and their relation with collagen remodeling.
abstract: In order to create tissue-engineered heart valves with long-term functionality, it is essential to fully understand collagen remodeling during neo-tissue formation. Collagen remodeling is thought to maintain mechanical tissue homeostasis. Yet, the driving factor of collagen remodeling remains unidentified. In this study, we determined the collagen architecture and the geometric and mechanical properties of human native semilunar heart valves of fetal to adult age using confocal microscopy, micro-indentation and inverse finite element analysis. The outcomes were used to predict age-dependent changes in stress and stretch in the heart valves via finite element modeling. The results indicated that the circumferential stresses are different between the aortic and pulmonary valve, and, moreover, that the stress increases considerably over time in the aortic valve. Strikingly, relatively small differences were found in stretch with time and between the aortic and pulmonary valve, particularly in the circumferential direction, which is the main determinant of the collagen fiber stretch. Therefore, we suggest that collagen remodeling in the human heart valve maintains a stretch-driven homeostasis. Next to these novel insights, the unique human data set created in this study provides valuable input for the development of numerical models of collagen remodeling and optimization of tissue engineering.
  
  
  CONCLUSIONS
  Annually, over 280,000 heart valve replacements are performed worldwide. Tissue engineering has the potential to provide valvular disease patients with living valve substitutes that can last a lifetime. Valve functionality is mainly determined by the collagen architecture. Hence, understanding collagen remodeling is crucial for creating tissue-engineered valves with long-term functionality. In this study, we determined the structural and material properties of human native heart valves of fetal to adult age to gain insight into the mechanical stimuli responsible for collagen remodeling. The age-dependent evolutionary changes in mechanical state of the native valve suggest that collagen remodeling in heart valves is a stretch-driven process.
authors.affiliation: Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands. Electronic address: P.J.A.Oomen@tue.nl.
authors.forename: P J A
authors.initials: PJA
authors.lastname: Oomen
authors.affiliation: Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands. Electronic address: S.Loerakker@tue.nl.
authors.forename: S
authors.initials: S
authors.lastname: Loerakker
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: van Geemen
authors.affiliation: Department of Mechanical Engineering, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Neggers
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, 2300RC Leiden, Netherlands.
authors.forename: M-J T H
authors.initials: MTH
authors.lastname: Goumans
authors.affiliation: Department of Cardiothoracic Surgery and Heart Valve Bank, Erasmus Medical Center, 3000CA Rotterdam, Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: van den Bogaerdt
authors.affiliation: Department of Cardiothoracic Surgery and Heart Valve Bank, Erasmus Medical Center, 3000CA Rotterdam, Netherlands.
authors.forename: A J J C
authors.initials: AJJC
authors.lastname: Bogers
authors.affiliation: Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands.
authors.forename: C V C
authors.initials: CVC
authors.lastname: Bouten
authors.affiliation: Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands.
authors.forename: F P T
authors.initials: FPT
authors.lastname: Baaijens
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000378:metabolism*; D005260:Female; D006351:Heart Valves / Q000254:growth & development*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D013314:Stress, Mechanical
chemical_list: D003094:Collagen
keywords: Biomechanics; Collagen remodeling; Heart valves; Tissue engineering