title: Engineered cartilage generated by nasal chondrocytes is responsive to physical forces resembling joint loading.
abstract: OBJECTIVE
  To determine whether engineered cartilage generated by nasal chondrocytes (ECN) is responsive to different regimens of loading associated with joint kinematics and previously shown to be stimulatory of engineered cartilage generated by articular chondrocytes (ECA).
  
  
  METHODS
  Human nasal and articular chondrocytes, harvested from 5 individuals, were expanded and cultured for 2 weeks into porous polymeric scaffolds. The resulting ECN and ECA were then maintained under static conditions or exposed to the following loading regimens: regimen 1, single application of cyclic deformation for 30 minutes; regimen 2, intermittent application of cyclic deformation for a total of 10 days, followed by static culture for 2 weeks; regimen 3, application of surface motion for a total of 10 days.
  
  
  RESULTS
  Prior to loading, ECN constructs contained significantly higher amounts of glycosaminoglycan (GAG) and type II collagen compared with ECA constructs. ECN responded to regimen 1 by increasing collagen and proteoglycan synthesis, to regimen 2 by increasing the accumulation of GAG and type II collagen as well as the dynamic modulus, and to regimen 3 by increasing the expression of superficial zone protein, at the messenger RNA level and the protein level, as well as the release of hyaluronan. ECA constructs were overall less responsive to all loading regimens, likely due to the lower extracellular matrix content.
  
  
  CONCLUSIONS
  Human ECN is responsive to physical forces resembling joint loading and can up-regulate molecules typically involved in joint lubrication. These findings should prompt future in vivo studies exploring the possibility of using nasal chondrocytes as a cell source for articular cartilage repair.
authors.affiliation: University Hospital Basel, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Candrian
authors.forename: D
authors.initials: D
authors.lastname: Vonwil
authors.forename: A
authors.initials: A
authors.lastname: Barbero
authors.forename: E
authors.initials: E
authors.lastname: Bonacina
authors.forename: S
authors.initials: S
authors.lastname: Miot
authors.forename: J
authors.initials: J
authors.lastname: Farhadi
authors.forename: D
authors.initials: D
authors.lastname: Wirz
authors.forename: S
authors.initials: S
authors.lastname: Dickinson
authors.forename: A
authors.initials: A
authors.lastname: Hollander
authors.forename: M
authors.initials: M
authors.lastname: Jakob
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Alini
authors.forename: M
authors.initials: M
authors.lastname: Heberer
authors.forename: I
authors.initials: I
authors.lastname: Martin
mesh_terms: D000328:Adult; D002358:Cartilage, Articular / Q000166:cytology / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology*; D024043:Collagen Type II / Q000502:physiology; D003470:Culture Media; D015870:Gene Expression / Q000502:physiology; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D000076002:Hyaluronan Synthases; D008875:Middle Aged; D009666:Nose / Q000166:cytology; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013314:Stress, Mechanical; D013499:Surface Properties; D023822:Tissue Engineering; D016474:Weight-Bearing / Q000502:physiology*; D000099158:Proteoglycan 4
chemical_list: D024043:Collagen Type II; D003470:Culture Media; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D011509:Proteoglycans; D012333:RNA, Messenger; C419197:PRG4 protein, human; D000099158:Proteoglycan 4; C523794:HAS1 protein, human; C101754:HAS2 protein, human