title: A numerical model to study mechanically induced initiation and progression of damage in articular cartilage.
abstract: OBJECTIVE
  Proteoglycan (PG) loss and surface roughening, early signs of osteoarthritis (OA), are likely preceded by softening of the ground substance and the collagen network. Insight in their relative importance to progression of OA may assist the development of treatment strategies for early OA. To support interpretation of experimental data, a numerical model is proposed that can predict damage progression in cartilage over time, as a consequence of excessive mechanical loading. The objective is to assess the interaction between ground substance softening and collagen fiber damage using this model.
  
  
  METHODS
  An established cartilage mechanics model is extended with the assumption that excessive strains may damage the ground substance or the collagen network, resulting in softening of the overstrained constituent. During subsequent loading cycles the strain may or may not cross a threshold, resulting in damage to stabilize or to progress. To evaluate how softening of the ground substance and collagen may interact, damage progression is computed when either one of them, or both together are allowed to occur during stepwise increased loading.
  
  
  RESULTS
  Softening in the ground substance was predicted to localize in the superficial and transitional zone and resulted in cartilage softening. Collagen damage was most prominent in the superficial zone, with more diffuse damage penetrating deeper into the tissue, resulting in adverse strain gradients. Effects were more pronounced if both constituents developed damage in parallel.
  
  
  CONCLUSIONS
  Ground substance softening and collagen damage have distinct effects on cartilage mechanopathology, and damage in either one of them may promote each other.
authors.affiliation: Department of Biomedical Engineering, Gem-Z 4.101, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands. Electronic address: s.m.hosseini@tue.nl.
authors.forename: S M
authors.initials: SM
authors.lastname: Hosseini
authors.affiliation: Department of Biomedical Engineering, Gem-Z 4.101, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands. Electronic address: w.wilson@tue.nl.
authors.forename: W
authors.initials: W
authors.lastname: Wilson
authors.affiliation: Department of Biomedical Engineering, Gem-Z 4.101, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands. Electronic address: k.ito@tue.nl.
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Biomedical Engineering, Gem-Z 4.101, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands. Electronic address: c.c.v.donkelaar@tue.nl.
authors.forename: C C
authors.initials: CC
authors.lastname: van Donkelaar
mesh_terms: D000465:Algorithms; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000737:chemistry / Q000293:injuries* / Q000503:physiopathology; D018450:Disease Progression; D024022:Fibrillar Collagens / Q000737:chemistry; D006801:Humans; D008954:Models, Biological; D010003:Osteoarthritis / Q000378:metabolism / Q000503:physiopathology*; D011509:Proteoglycans / Q000502:physiology; D013314:Stress, Mechanical; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D024022:Fibrillar Collagens; D011509:Proteoglycans
keywords: Cartilage softening; Collagen damage; Damage mechanics; Osteoarthritis