title: Stress related collagen ultrastructure in human aortic valves--implications for tissue engineering.
abstract: Understanding the response of tissue structures to mechanical stress is crucial for optimization of mechanical conditioning protocols in the field of heart valve tissue engineering. In heart valve tissue, it is unclear to what extent mechanical loading affects the collagen fibril morphology. To determine if local stress affects the collagen fibril morphology, in terms of fibril diameter, its distribution, and the fibril density, this was investigated in adult native human aortic valve leaflets. Transmission electron microscopy images of collagen fibrils were analyzed at three locations: the commissures, the belly, and the fixed edge of the leaflets. Subsequently, the mechanical behavior of human aortic valves was used in a computational model to predict the stress distribution in the valve leaflet during the diastolic phase of the cardiac cycle. The local stresses at the three locations were related to the collagen fibril morphology. The fibril diameter and density varied significantly between the measured locations, and appeared inversely related. The average fibril diameter increased from the fixed edge, to the belly, and to the commissures of the leaflets, while fibril density decreased. Interestingly, these differences corresponded well with the level of stress at the locations. The presented data showed that large tissue stress is associated with greater average fibril diameter, lower fibril density, and wider fibril size distribution compared with low stress locations in the leaflets. The findings here provide insight in the effect of mechanical loading on the collagen ultrastructure, and are valuable to improve conditioning protocols for tissue engineering.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands. a.balguid@tue.nl
authors.forename: Angelique
authors.initials: A
authors.lastname: Balguid
authors.forename: Niels J B
authors.initials: NJ
authors.lastname: Driessen
authors.forename: Anita
authors.initials: A
authors.lastname: Mol
authors.forename: Joep P J
authors.initials: JP
authors.lastname: Schmitz
authors.forename: Fons
authors.initials: F
authors.lastname: Verheyen
authors.forename: Carlijn V C
authors.initials: CV
authors.lastname: Bouten
authors.forename: Frank P T
authors.initials: FP
authors.lastname: Baaijens
mesh_terms: D001021:Aortic Valve / Q000502:physiology* / Q000648:ultrastructure*; D001705:Bioprosthesis; D003198:Computer Simulation; D055119:Elastic Modulus; D005260:Female; D024022:Fibrillar Collagens / Q000502:physiology* / Q000648:ultrastructure*; D006350:Heart Valve Prosthesis; D006801:Humans; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008875:Middle Aged; D008955:Models, Cardiovascular; D011487:Protein Conformation; D013314:Stress, Mechanical; D023822:Tissue Engineering
chemical_list: D024022:Fibrillar Collagens