title: Rheological and dynamic integrity of simulated degenerated disc and consequences after cross-linker augmentation.
abstract: METHODS
  An in situ study using whole-organ culture system.
  
  
  OBJECTIVE
  To study the effect of disc degeneration at different stages on its rheological and dynamic properties and to investigate the efficacy of exogenous cross-linking therapy.
  
  
  BACKGROUND
  Disc degeneration can involve protein denaturation or microdefects to the disc's collagen fiber network. A disc degeneration model using whole-organ culture technique can be effectively used for the screening of treatments of degenerated discs. Exogenous cross-linking therapy has been shown to enhance the mechanical properties of the disc by cross-linking collagen. However, the efficacy of this therapy on the degenerated disc is unclear.
  
  
  METHODS
  A total of 40 porcine thoracic discs were assigned to 5 groups: intact discs, moderately degenerated discs, moderately degenerated discs with cross-linker augmentation, severely degenerated discs, and severely degenerated discs with cross-linker augmentation. The disc degeneration was simulated by trypsin digestion and mechanical fatigue loading. Rheological properties, dynamic properties, water content, and histological analysis were conducted after a 7-day incubation.
  
  
  RESULTS
  The mechanical properties of moderate degenerated discs significantly decrease both in rheological and dynamic properties, and laminate structure disorganization was observed. Mechanical defects of severely degenerated discs resulted in disc height loss, an increase in the aggregate modulus and stiffness modulus, and a decrease in the damping coefficient, hydraulic permeability, and water content. Cross-linker augmentation significantly recovered mechanical properties of moderately degenerated discs and restored the water content compared with the intact disc. However, the augmentation did not fully repair the severely degenerated discs.
  
  
  CONCLUSIONS
  Trypsin-induced extracellular matrix damage resulted in a change of the disc's biomechanics. Cross-linker augmentation recovers the rheological and dynamic properties of moderately degenerated discs but not of the severely degenerated discs. The genipin cross-linker may be able to improve the proteoglycan depletion effect in the nucleus pulposus but may not be effective to restore the structural damage in the collagen molecule of the anulus fibrosus.
authors.affiliation: *Institute of Biomedical Engineering, College of Medicine and Engineering, National Taiwan University, Taipei, Taiwan; and †School of Mechanical Engineering, Iran University of Science and Technology, Tehran, Iran; **Department of Mechanical Engineering, College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Hsu
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Kuo
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Chang
authors.forename: Mohammad
authors.initials: M
authors.lastname: Nikkhoo
authors.forename: Jaw-Lin
authors.initials: JL
authors.lastname: Wang
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003094:Collagen / Q000378:metabolism; D003198:Computer Simulation; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D039823:Iridoids / Q000494:pharmacology*; D008954:Models, Biological; D009924:Organ Culture Techniques; D019637:Orthopedic Procedures; D011509:Proteoglycans / Q000378:metabolism; D012212:Rheology; D012720:Severity of Illness Index; D013314:Stress, Mechanical; D013552:Swine; D013904:Thoracic Vertebrae / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome; D014357:Trypsin / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D039823:Iridoids; D011509:Proteoglycans; D003094:Collagen; C007834:genipin; D014357:Trypsin